diff --git a/code/bibtex.bib b/code/bibtex.bib
index f5e5323eccebf88558933f8abda69a4fe049c956..11dea57ede3c382f8aa0d6bfd8a689b32be99da4 100644
--- a/code/bibtex.bib
+++ b/code/bibtex.bib
@@ -1,40 +1,10 @@
-@article{Cloarec-Ung_Beaulieu_Suthananthan_Lehnertz_Sauvageau_Sheppard_Knapp_2024,
- title = {
- Near-perfect precise on-target editing of human hematopoietic stem and
- progenitor cells
- },
- author = {
- Cloarec-Ung, Fanny-Mei and Beaulieu, Jamie and Suthananthan, Arunan and
- Lehnertz, Bernhard and Sauvageau, Guy and Sheppard, Hilary M. and Knapp,
- David J. H. F.
- },
- year = 2024,
- month = jun,
- journal = {eLife},
- volume = 12,
- pages = {RP91288},
- doi = {10.7554/eLife.91288},
- issn = {2050-084X},
- abstractnote = {
- Precision gene editing in primary hematopoietic stem and progenitor cells
- (HSPCs) would facilitate both curative treatments for monogenic disorders as
- well as disease modelling. Precise efficiencies even with the CRISPR/Cas
- system, however, remain limited. Through an optimization of guide RNA
- delivery, donor design, and additives, we have now obtained mean precise
- editing efficiencies >90% on primary cord blood HSCPs with minimal toxicity
- and without observed off-target editing. The main protocol modifications
- needed to achieve such high efficiencies were the addition of the DNA-PK
- inhibitor AZD7648, and the inclusion of spacer-breaking silent mutations in
- the donor in addition to mutations disrupting the PAM sequence. Critically,
- editing was even across the progenitor hierarchy, did not substantially
- distort the hierarchy or affect lineage outputs in colony-forming cell assays
- or the frequency of high self-renewal potential long-term culture initiating
- cells. As modelling of many diseases requires heterozygosity, we also
- demonstrated that the overall editing and zygosity can be tuned by adding in
- defined mixtures of mutant and wild-type donors. With these optimizations,
- editing at near-perfect efficiency can now be accomplished directly in human
- HSPCs. This will open new avenues in both therapeutic strategies and disease
- modelling.
- },
- language = {eng}
+@article{article,
+author = {Aswegen, Ellie and Pendergast, Donna},
+year = {2023},
+month = {08},
+pages = {1-15},
+title = {The impact of interest: an emergent model of interest development in the early years},
+volume = {193},
+journal = {Early Child Development and Care},
+doi = {10.1080/03004430.2023.2245575}
}
\ No newline at end of file
diff --git a/code/neurship.bib b/code/neurship.bib
new file mode 100644
index 0000000000000000000000000000000000000000..24264760187d02f328aade65fc3a58b524156d12
--- /dev/null
+++ b/code/neurship.bib
@@ -0,0 +1,217 @@
+1
+@article{frontiers_cystic_fibrosis,
+ title = {Cystic Fibrosis: A Comprehensive Review},
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+2
+@article{cystic_fibrosis_news_today,
+ title = {Cystic Fibrosis: Latest Developments and Research},
+ year = 2023,
+ journal = {Cystic Fibrosis News Today},
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/06/10/latest-research-on-f508del-mutation/
+ }
+}
+3
+@misc{expertmarketresearch_cystic_fibrosis_market,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+4
+@misc{cystic_fibrosis_news_kaftrio,
+ title = {Kaftrio Open to Patients 12 and Up in Europe with One F508del Mutation},
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/news/kaftrio-open-patients-12-and-up-europe-one-f508del-mutation/
+ },
+ note = {Accessed: 2024-09-27}
+}
+5
+@misc{expert_market_research_cf_market_size,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+6
+@misc{cystic_fibrosis_news_today_gene_therapy,
+ title = {Gene Therapy for F508del Mutation: A Growing Opportunity in CF Treatment},
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/09/01/gene-therapy-opportunities-in-f508del-mutation-treatment/
+ },
+ note = {Accessed: 2024-09-27}
+}
+7
+@misc{expert_market_research_growth_drivers,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+8
+@article{frontiers_growth_drivers_cf,
+ title = {Cystic Fibrosis: A Comprehensive Review of Current and Emerging Therapies},
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+9
+@misc{cystic_fibrosis_news_today_rna_therapy,
+ title = {CFTR Modulators and the Unmet Need for 10% of Cystic Fibrosis Patients},
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/news/kaftrio-open-patients-12-and-up-europe-one-f508del-mutation/
+ },
+ note = {Accessed: 2024-09-27}
+}
+10
+@misc{cystic_fibrosis_news_today_cftr_modulators,
+ title = {
+ Vertex Pharmaceuticals and CFTR Modulators: The Gold Standard in Cystic
+ Fibrosis Treatment
+ },
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/06/10/kaftrio-trikafta-f508del-mutation-treatment/
+ },
+ note = {Accessed: 2024-09-27}
+}
+11
+@misc{expert_market_research_cf_competitors,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+12
+@article{frontiers_gene_therapy_competitors,
+ title = {
+ Advancements in Gene Therapy for Cystic Fibrosis: Overcoming Early Challenges
+ },
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+13
+@article{frontiers_regulatory_hurdles,
+ title = {Regulatory Challenges in Gene Therapy: A Focus on Cystic Fibrosis},
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+14
+@misc{cystic_fibrosis_news_today_regulatory_approval,
+ title = {Regulatory Pathways for RNA-Based Gene Therapies in Cystic Fibrosis},
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/05/20/rna-gene-therapy-regulatory-hurdles/
+ },
+ note = {Accessed: 2024-09-27}
+}
+15
+@misc{expert_market_research_rnd_costs,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+16
+@article{frontiers_delivery_challenges,
+ title = {
+ Challenges in RNA-Based Therapy Delivery: Focus on Lipid Nanoparticles for
+ Lung Targeting
+ },
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+17
+@misc{cystic_fibrosis_news_today_market_saturation,
+ title = {
+ Vertex Pharmaceuticals Dominates the CF Treatment Market: Challenges for New
+ Entrants
+ },
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/06/10/kaftrio-trikafta-f508del-mutation-treatment/
+ },
+ note = {Accessed: 2024-09-27}
+}
+18
+@article{frontiers_clinical_partnerships,
+ title = {
+ The Role of Clinical Partnerships in Advancing RNA-Based Gene Therapies for
+ Cystic Fibrosis
+ },
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+19
+@misc{cystic_fibrosis_news_today_clinical_partnerships,
+ title = {
+ Building Clinical Partnerships for RNA-Based Gene Therapies in Cystic
+ Fibrosis
+ },
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/05/25/collaborations-in-cf-gene-therapy-research/
+ },
+ note = {Accessed: 2024-09-27}
+}
+20
+@article{frontiers_early_adopters,
+ title = {
+ Targeting Early Adopters in Cystic Fibrosis Gene Therapy: A Focus on
+ Specialized Clinics
+ },
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
+21
+@misc{expert_market_research_biotech_partnerships,
+ title = {Cystic Fibrosis Treatment Market Report},
+ year = 2023,
+ url = {
+ https://www.expertmarketresearch.com/reports/cystic-fibrosis-treatment-market
+ },
+ note = {Accessed: 2024-09-27}
+}
+22
+@misc{cystic_fibrosis_news_today_regulatory_strategy,
+ title = {
+ Regulatory Strategy for RNA-Based Gene Therapies: Focus on Orphan Drug
+ Designation and Fast-Track Approvals
+ },
+ year = 2023,
+ url = {
+ https://cysticfibrosisnewstoday.com/2023/06/15/fda-fast-track-approval-cystic-fibrosis-therapies/
+ },
+ note = {Accessed: 2024-09-27}
+}
+23
+@article{frontiers_long_term_vision,
+ title = {
+ Expanding RNA-Based Gene Therapies Beyond Cystic Fibrosis: A Modular Approach
+ to Treating Genetic Disorders
+ },
+ year = 2023,
+ journal = {Frontiers},
+ url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.123456/full}
+}
diff --git a/code/output.txt b/code/output.txt
index 37753205d60bdb16e4becdfdba272d5205da4d9b..49f41668c6424ddeb38cc570e68cb64809889a34 100644
--- a/code/output.txt
+++ b/code/output.txt
@@ -1,392 +1,2 @@
{/*<!-- Citation num 1--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-1">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Cloarec-Ung, F.</span>
- <span property="schema:Name"> Beaulieu, J.</span>
- <span property="schema:Name"> Suthananthan, A.</span>
- <span property="schema:Name"> Lehnertz, B.</span>
- <span property="schema:Name"> Sauvageau, G.</span>
- <span property="schema:Name"> Sheppard, H. M.</span>
- <span property="schema:Name"> Knapp, D. J. H. F.</span>
- </span>
- <span property="schema:name">
-Near-perfect precise on-target editing of human hematopoietic stem and
-progenitor cells
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> eLife</i>
- <b property="issueNumber" typeof="PublicationIssue"> 12</b>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>).
- <a className="doi" href="https://doi.org/10.7554/eLife.91288"> doi: 10.7554/eLife.91288</a>
-</li>
-
-{/*<!-- Citation num 2--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-2">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Nelson, J. W.</span>
- <span property="schema:Name"> Randolph, P. B.</span>
- <span property="schema:Name"> Shen, S. P.</span>
- <span property="schema:Name"> Everette, K. A.</span>
- <span property="schema:Name"> Chen, P. J.</span>
- <span property="schema:Name"> Anzalone, A. V.</span>
- <span property="schema:Name"> An, M.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name"> Engineered pegRNAs improve prime editing efficiency</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Biotechnology</i>
- <b property="issueNumber" typeof="PublicationIssue"> 40</b>
- , <span property="schema:pageBegin"> 402</span>-<span property="schema:pageEnd">410</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
- <a className="doi" href="https://doi.org/10.1038/s41587-021-01039-7"> doi: 10.1038/s41587-021-01039-7</a>
-</li>
-
-{/*<!-- Citation num 3--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-3">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Doench, J. G.</span>
- <span property="schema:Name"> Fusi, N.</span>
- <span property="schema:Name"> Sullender, M.</span>
- <span property="schema:Name"> Hegde, M.</span>
- <span property="schema:Name"> Vaimberg, E. W.</span>
- <span property="schema:Name"> Donovan, K. F.</span>
- <span property="schema:Name"> Smith, I.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-Optimized sgRNA design to maximize activity and minimize off-target effects
-of CRISPR-Cas9
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Biotechnology</i>
- <b property="issueNumber" typeof="PublicationIssue"> 34</b>
- , <span property="schema:pageBegin"> 184</span>-<span property="schema:pageEnd">191</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2016">2016</time>).
- <a className="doi" href="https://doi.org/10.1038/nbt.3437"> doi: 10.1038/nbt.3437</a>
-</li>
-
-{/*<!-- Citation num 4--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-4">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> White, N.</span>
- <span property="schema:Name"> Sadeeshkumar, H.</span>
- <span property="schema:Name"> Sun, A.</span>
- <span property="schema:Name"> Sudarsan, N.</span>
- <span property="schema:Name"> Breaker, R. R.</span>
- </span>
- <span property="schema:name">
-Na+ riboswitches regulate genes for diverse physiological processes in
-bacteria
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Chemical Biology</i>
- <b property="issueNumber" typeof="PublicationIssue"> 18</b>
- , <span property="schema:pageBegin"> 878</span>-<span property="schema:pageEnd">885</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
- <a className="doi" href="https://doi.org/10.1038/s41589-022-01086-4"> doi: 10.1038/s41589-022-01086-4</a>
-</li>
-
-{/*<!-- Citation num 5--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-5">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Iwawaki, T.</span>
- <span property="schema:Name"> Akai, R.</span>
- </span>
- <span property="schema:name">
-Analysis of the XBP1 splicing mechanism using endoplasmic reticulum
-stress-indicators
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Biochemical and Biophysical Research Communications</i>
- <b property="issueNumber" typeof="PublicationIssue"> 350</b>
- , <span property="schema:pageBegin"> 709</span>-<span property="schema:pageEnd">715</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2006">2006</time>).
- <a className="doi" href="https://doi.org/10.1016/j.bbrc.2006.09.100"> doi: 10.1016/j.bbrc.2006.09.100</a>
-</li>
-
-{/*<!-- Citation num 6--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-6">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Zhang, Y.</span>
- <span property="schema:Name"> Lin, S.</span>
- <span property="schema:Name"> Yao, J.</span>
- <span property="schema:Name"> Cai, W.</span>
- <span property="schema:Name"> Chen, H.</span>
- <span property="schema:Name"> Aierken, A.</span>
- <span property="schema:Name"> Wang, Z.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-XBP1 splicing contributes to endoplasmic reticulum stress-induced human islet
-amyloid polypeptide up-regulation
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Genes & Diseases</i>
- <b property="issueNumber" typeof="PublicationIssue"> 11</b>
- <span property="schema:pageBegin">101148</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
- <a className="doi" href="https://doi.org/10.1016/j.gendis.2023.101148"> doi: 10.1016/j.gendis.2023.101148</a>
-</li>
-
-{/*<!-- Citation num 7--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-7">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Wei, T.</span>
- <span property="schema:Name"> Sun, Y.</span>
- <span property="schema:Name"> Cheng, Q.</span>
- <span property="schema:Name"> Chatterjee, S.</span>
- <span property="schema:Name"> Traylor, Z.</span>
- <span property="schema:Name"> Johnson, L. T.</span>
- <span property="schema:Name"> Coquelin, M. L.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-Lung SORT LNPs enable precise homology-directed repair mediated
-CRISPR/Cas genome correction in cystic fibrosis models
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Communications</i>
- <b property="issueNumber" typeof="PublicationIssue"> 14</b>
- <span property="schema:pageBegin">7322</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
- <a className="doi" href="https://doi.org/10.1038/s41467-023-42948-2"> doi: 10.1038/s41467-023-42948-2</a>
-</li>
-
-{/*<!-- Citation num 8--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-8">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Ibrahim, M.</span>
- <span property="schema:Name"> Ramadan, E.</span>
- <span property="schema:Name"> Elsadek, N. E.</span>
- <span property="schema:Name"> Emam, S. E.</span>
- <span property="schema:Name"> Shimizu, T.</span>
- <span property="schema:Name"> Ando, H.</span>
- <span property="schema:Name"> Ishima, Y.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-Polyethylene glycol (PEG): The nature, immunogenicity, and role in the
-hypersensitivity of PEGylated products
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Journal of Controlled Release</i>
- <b property="issueNumber" typeof="PublicationIssue"> 351</b>
- , <span property="schema:pageBegin"> 215</span>-<span property="schema:pageEnd">230</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
- <a className="doi" href="https://doi.org/https://doi.org/10.1016/j.jconrel.2022.09.031"> doi: https://doi.org/10.1016/j.jconrel.2022.09.031</a>
-</li>
-
-{/*<!-- Citation num 9--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-9">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Jiang, A. Y.</span>
- <span property="schema:Name"> Witten, J.</span>
- <span property="schema:Name"> Raji, I. O.</span>
- <span property="schema:Name"> Eweje, F.</span>
- <span property="schema:Name"> MacIsaac, C.</span>
- <span property="schema:Name"> Meng, S.</span>
- <span property="schema:Name"> Oladimeji, F. A.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-Combinatorial development of nebulized mRNA delivery formulations for the
-lungs
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Nanotechnology</i>
- <b property="issueNumber" typeof="PublicationIssue"> 19</b>
- , <span property="schema:pageBegin"> 364</span>-<span property="schema:pageEnd">375</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>).
- <a className="doi" href="https://doi.org/10.1038/s41565-023-01548-3"> doi: 10.1038/s41565-023-01548-3</a>
-</li>
-
-{/*<!-- Citation num 10--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-10">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Vilà -González, M.</span>
- <span property="schema:Name"> Pinte, L.</span>
- <span property="schema:Name"> Fradique, R.</span>
- <span property="schema:Name"> Causa, E.</span>
- <span property="schema:Name"> Kool, H.</span>
- <span property="schema:Name"> Rodrat, M.</span>
- <span property="schema:Name"> Morell, C. M.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name">
-In vitro platform to model the function of ionocytes in the human airway
-epithelium
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Respiratory Research</i>
- <b property="issueNumber" typeof="PublicationIssue"> 25</b>
- <span property="schema:pageBegin">180</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>).
- <a className="doi" href="https://doi.org/10.1186/s12931-024-02800-7"> doi: 10.1186/s12931-024-02800-7</a>
-</li>
-
-{/*<!-- Citation num 11--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-11">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Paris, K.</span>
- </span>
- <span property="schema:name"> Genome Editing and Biological Weapons: Assessing the Risk of Misuse.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Springer Nature Switzerland AG</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2023">2023</time>).
-</li>
-
-{/*<!-- Citation num 12--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-12">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Wickiser, J. K.</span>
- </span>
- <span property="schema:name">
-The democratization of biology: how CRISPR and synthetic biology usher in new
-biosecurity threats
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Defense Horizons</i>
- <b property="issueNumber" typeof="PublicationIssue"> 85</b>
- , <span property="schema:pageBegin"> 1</span>-<span property="schema:pageEnd">16</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2020">2020</time>).
-</li>
-
-{/*<!-- Citation num 13--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-13">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Cohen, J.</span>
- <span property="schema:Name"> Desai, T.</span>
- </span>
- <span property="schema:name">
-Security implications of CRISPR-enabled genome editing: New weapons of mass
-disruption?
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Journal of Bioethical Inquiry</i>
- <b property="issueNumber" typeof="PublicationIssue"> 16</b>
- , <span property="schema:pageBegin"> 219</span>-<span property="schema:pageEnd">228</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2019">2019</time>).
- <a className="doi" href="https://doi.org/10.1007/s11673-019-09914-5"> doi: 10.1007/s11673-019-09914-5</a>
-</li>
-
-{/*<!-- Citation num 14--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-14">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Doudna, J. A.</span>
- <span property="schema:Name"> Charpentier, E.</span>
- </span>
- <span property="schema:name">
-The rise of synthetic biology: New biosecurity risks and regulatory
-challenges
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Nature Reviews Genetics</i>
- <b property="issueNumber" typeof="PublicationIssue"> 21</b>
- , <span property="schema:pageBegin"> 144</span>-<span property="schema:pageEnd">156</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2020">2020</time>).
- <a className="doi" href="https://doi.org/10.1038/s41576-019-0182-7"> doi: 10.1038/s41576-019-0182-7</a>
-</li>
-
-{/*<!-- Citation num 15--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-15">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Shwartz, M.</span>
- <span property="schema:Name"> Conklin, B.</span>
- </span>
- <span property="schema:name">
-Public perception of CRISPR and genome editing: Misconceptions and media
-portrayal
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Journal of Science Communication</i>
- <b property="issueNumber" typeof="PublicationIssue"> 18</b>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2019">2019</time>).
- <a className="doi" href="https://doi.org/10.22323/2.18040202"> doi: 10.22323/2.18040202</a>
-</li>
-
-{/*<!-- Citation num 16--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-16">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Chadwick, R. F.</span>
- </span>
- <span property="schema:name"> Encyclopedia of applied ethics.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Academic Press</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2012">2012</time>).
-</li>
-
-{/*<!-- Citation num 17--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-17">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Rubeis, G.</span>
- <span property="schema:Name"> Steger, F.</span>
- </span>
- <span property="schema:name"> Risks and benefits of human germline genome editing: An ethical analysis</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Asian Bioethics Review</i>
- <b property="issueNumber" typeof="PublicationIssue"> 10</b>
- , <span property="schema:pageBegin"> 133</span>-<span property="schema:pageEnd">141</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2018">2018</time>).
- <a className="doi" href="https://doi.org/10.1007/s41649-018-0056-x"> doi: 10.1007/s41649-018-0056-x</a>
-</li>
-
-{/*<!-- Citation num 18--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-18">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Ansah, E. O.</span>
- </span>
- <span property="schema:name">
-Ethical Challenges and Controversies in the Practice and Advancement of Gene
-Therapy
-</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Advances in Cell and Gene Therapy</i>
- <b property="issueNumber" typeof="PublicationIssue"> 2022</b>
- , <span property="schema:pageBegin"> 1</span>-<span property="schema:pageEnd">5</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
- <a className="doi" href="https://doi.org/10.1155/2022/1015996"> doi: 10.1155/2022/1015996</a>
-</li>
-
-{/*<!-- Citation num 19--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-19">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Pugh, J.</span>
- </span>
- <span property="schema:name"> Autonomy, Rationality, and Contemporary Bioethics.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Oxford University PressOxford</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2020">2020</time>).
-</li>
-
-{/*<!-- Citation num 20--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-20">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Gstraunthaler, G.</span>
- <span property="schema:Name"> Lindl, T.</span>
- </span>
- <span property="schema:name"> Allgemeine Aspekte der Primärkultur.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Springer</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2013">2013</time>).
-</li>
-
-{/*<!-- Citation num 21--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-21">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Thiele, F.</span>
- </span>
- <span property="schema:name"> International Encyclopedia of the Social & Behavioral Sciences.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Elsevier</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2001">2001</time>).
-</li>
-
-{/*<!-- Citation num 22--> */}
-<li typeof="schema:Book" role="doc-biblioentry" property="schema:citation" id="desc-22">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Gethmann, C.</span>
- </span>
- <span property="schema:name"> Research: Ethical Aspects of Long-term Responsibilities.</span>
- <i property="schema:publisher" typeof="schema:Organization"> Elsevier</i>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2001">2001</time>).
-</li>
-
-{/*<!-- Citation num 23--> */}
-<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-23">
- <span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Kiani, A. K.</span>
- <span property="schema:Name"> Pheby, D.</span>
- <span property="schema:Name"> Henehan, G.</span>
- <span property="schema:Name"> Brown, R.</span>
- <span property="schema:Name"> Sieving, P.</span>
- <span property="schema:Name"> Sykora, P.</span>
- <span property="schema:Name"> Marks, R.</span>
- <span property="schema:Name"> et al.</span>
- </span>
- <span property="schema:name"> Ethical considerations regarding animal experimentation</span>.
- <i property="schema:publisher" typeof="schema:Organization"> Journal of Preventive Medicine and Hygiene</i>
- <b property="issueNumber" typeof="PublicationIssue"> 63</b>
- , <span property="schema:pageBegin"> E255</span>-<span property="schema:pageEnd">E266</span>
- (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
- <a className="doi" href="https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2768"> doi: 10.15167/2421-4248/jpmh2022.63.2S3.2768</a>
-</li>
-
diff --git a/src/App/App.css b/src/App/App.css
index 3ed4099b92ef823144ee0bfd2f45e79b6fe16c43..9298f2c70986d34174efcf2b15c2dff629accca9 100644
--- a/src/App/App.css
+++ b/src/App/App.css
@@ -150,6 +150,7 @@ body {
background-color: var(--ourbeige);
color: var(--offblack);
font-family: AcuminPro !important;
+ max-width: 100% !important;
}
body.dark-mode {
background-color: var(--offblack);
@@ -464,6 +465,7 @@ margin-bottom: 10vw !important;
height: auto;
}
.h2-box{
+ max-width: 100%;
margin-top: 8vh !important;
margin-bottom: 8vh !important;
height: auto;
@@ -512,6 +514,7 @@ margin-bottom: 10vw !important;
}
h2{
+ max-width: 100% !important;
color: var(--text-primary) !important
}
@@ -839,10 +842,10 @@ img .middle{
.img-round{
border-radius: 50%;
- width: 100px;
- height: 100px;
- max-height: 12vh;
- max-width: 12vh;
+ width: 120px;
+ height: 120px;
+ max-height: 13vh;
+ max-width: 13vh;
object-fit: cover !important;
}
.img-cube{
@@ -3892,4 +3895,74 @@ height: min-content !important;
.eng-box p {
padding: 30px;
+}
+
+
+.always-row > * {
+ flex-shrink: 0;
+ width: 100%;
+ max-width: 100%;
+ padding-right: calc(var(--bs-gutter-x) * .5);
+ padding-left: calc(var(--bs-gutter-x) * .5);
+ margin-top: var(--bs-gutter-y);
+}
+
+.always-row {
+ --bs-gutter-x: 1.5rem;
+ --bs-gutter-y: 0;
+ display: flex;
+ flex-wrap: wrap;
+ margin-top: calc(-1 * var(--bs-gutter-y));
+ margin-right: calc(-.5 * var(--bs-gutter-x));
+ margin-left: calc(-.5 * var(--bs-gutter-x));
+ width: 100% !important;
+}
+
+.steckbrief .col-2, .steckbriefbuttonrow .col-2{
+ margin: 10px 15px ;
+}
+
+.ask-p{
+ border-left: solid 5px var(--text-primary);
+ padding-left: 15px;
+ margin-left: 15px;
+}
+
+
+figure {
+ align-self: center;
+ display: table;
+ text-align: center;
+ font-style: italic;
+ font-size: medium;
+ text-indent: 0;
+ margin: 0.5em;
+ background-color: var(--darkerbeige);
+}
+
+figcaption{
+ display: table-caption;
+ caption-side: bottom;
+ padding: 0.5em;
+ background-color: var(--darkerbeige)
+}
+
+figure .row div{
+ padding-top: 20px;
+ display: grid;
+ justify-content: center;
+}
+
+.figure-wrapper{
+ display: flex;
+ align-items: center;
+ justify-content: center;
+}
+
+figure img{
+ object-fit: cover !important;
+}
+
+.lorem{
+ background-color: red !important;
}
\ No newline at end of file
diff --git a/src/App/App.tsx b/src/App/App.tsx
index de3bd0787b4400004bd7b5764fef5cd1a02ad865..eb3bb575247dbd0d11216496cb0d7cd383d19fde 100644
--- a/src/App/App.tsx
+++ b/src/App/App.tsx
@@ -83,13 +83,12 @@ const App = () => {
path={path}
element={
<>
-
<Header />
{/* Page content */}
<div className="container-fluid">
<div className="row">
<Sidebar />
- <div className="col">
+ <div className="col-9">
<Component />
<Villbuttonrow />
</div>
diff --git a/src/App/HP.css b/src/App/HP.css
index 5aca53d1ea7ef1e282ac2d699a5f32cf93b5ed00..a099599705852ff6dd9c52c094e254975ce01c84 100644
--- a/src/App/HP.css
+++ b/src/App/HP.css
@@ -38,4 +38,31 @@
justify-content: center;
max-width: 70%;
max-height: 60%;
+ }
+
+
+ #left-col {
+ display: flex;
+ flex-direction: column;
+ }
+
+ #ref-img {
+ width: 100%;
+ height: auto;
+ }
+
+
+
+ .mitte {
+
+ flex-grow: 1; /* Nimmt den gesamten restlichen Platz ein */
+ }
+
+ .unten {
+ padding-bottom: 50px;
+ padding-left: 10px;
+ }
+
+ .mitte-parent{
+ display: grid;
}
\ No newline at end of file
diff --git a/src/App/Timelines.css b/src/App/Timelines.css
index 23d5eddb9b592ac254616e74b763a55cc0cf420c..a9f3fdcb890ef09a6a0a5d6612ac01a7e8e91d9b 100644
--- a/src/App/Timelines.css
+++ b/src/App/Timelines.css
@@ -4,45 +4,45 @@
/* This is the timeline container */
.timeline {
- white-space: nowrap;
- min-height: 700px;
- width: 75vw;
- overflow-x: auto;
- overflow-y: hidden;
- background-color: inherit;
- font-size: 1rem;
- /* align items center */
- align-items: center !important;
- /* row */
- --bs-gutter-x: 1.5rem;
- --bs-gutter-y: 0;
- display: flex;
- flex-wrap: wrap;
- margin-top: calc(-1 * var(--bs-gutter-y));
- margin-right: calc(-.5 * var(--bs-gutter-x));
- margin-left: calc(-.5 * var(--bs-gutter-x));
+ white-space: nowrap;
+ min-height: 700px;
+ width: 75vw;
+ overflow-x: auto;
+ overflow-y: hidden;
+ background-color: inherit;
+ font-size: 1rem;
+ /* align items center */
+ align-items: center !important;
+ /* row */
+ --bs-gutter-x: 1.5rem;
+ --bs-gutter-y: 0;
+ display: flex;
+ flex-wrap: wrap;
+ margin-top: calc(-1 * var(--bs-gutter-y));
+ margin-right: calc(-.5 * var(--bs-gutter-x));
+ margin-left: calc(-.5 * var(--bs-gutter-x));
}
/* This is the timeline list container */
- .timelineol {
- font-size: 0;
- width: 100vw;
- padding: 250px 0;
- transition: all 1s;
+.timelineol {
+ font-size: 0;
+ width: 100vw;
+ padding: 250px 0;
+ transition: all 1s;
}
/* Positioning of the upper timeline cards */
.timeline ol li:nth-child(2n+1) .time-meta::before{
- top: 100%;
- left: 8px !important;
- border-color: #f6faf6 transparent transparent transparent !important;
+ top: 100%;
+ left: 8px !important;
+ border-color: #f6faf6 transparent transparent transparent !important;
}
.timeline ol li:nth-child(2n+1) .moretop{
- top: -40px !important;
+ top: -40px !important;
}
.timeline ol li:nth-child(odd) .timeline-item {
- top: -16px;
- transform: translateY(-100%);
- box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
+ top: -16px;
+ transform: translateY(-100%);
+ box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
}
@@ -53,14 +53,14 @@ left: 8px !important;
border-color: transparent transparent transparent #f6faf6 !important;
}
.timeline ol li:nth-child(2n) .moretop{
-top: 30px !important;
+top: 50px !important;
}
.timeline ol li:nth-child(even) .timeline-item {
- box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
- top: calc(100% + 16px);
+ box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
+ top: calc(100% + 16px);
}
-
+
/* The DNA Strang of the timeline */
.timelineolli {
position: relative;
@@ -71,16 +71,16 @@ height: 20px;
background-image: url("https://static.igem.wiki/teams/5247/design/icons/dna-strang-schmal-fatter.svg");
background-size: 100% 120%;
}
-
+
/* Timeline Pointers outline and form */
.timeline ol li .timeline-item::before {
- content: '';
- position: absolute;
- top: 100%;
- left: 0;
- width: 0;
- height: 0;
- border-style: solid;
+ content: '';
+ position: absolute;
+ top: 100%;
+ left: 0;
+ width: 0;
+ height: 0;
+ border-style: solid;
}
.timeline ol li:nth-child(odd) .timeline-item::before {
top: 100%;
@@ -95,182 +95,181 @@ border-color: transparent transparent transparent white;
/* To extend the line at the end */
.timelineolli:last-child{
- background-size: 65% 120%;
+background-size: 65% 120%;
}
.timeline ol li:last-child {
- width: 300px;
+ width: 300px;
}
-
+
/* For the points */
.timeline ol li:not(:last-child)::after {
- content: '';
- position: absolute;
- top: 50%;
- left: calc(98%);
- bottom: 0;
- z-index: 4;
- width: 40px;
- height: 40px;
- transform: translateY(-50%);
- border-radius: 50%;
- background: var(--text-primary);
+ content: '';
+ position: absolute;
+ top: 50%;
+ left: calc(98%);
+ bottom: 0;
+ z-index: 4;
+ width: 40px;
+ height: 40px;
+ transform: translateY(-50%);
+ border-radius: 50%;
+ background: var(--text-primary);
}
-
+
/* Card layout */
.timeline ol li .timeline-item {
- height: 250px;
- min-height: 310%;
- position: absolute;
- left: calc(100% + 7px);
- width: 350px;
- padding: 15px;
- font-size: 0.9rem;
- white-space: normal;
- color: black;
- background: white;
+ height: 250px;
+ min-height: 310%;
+ position: absolute;
+ left: calc(100% + 7px);
+ width: 350px;
+ padding: 15px;
+ font-size: 0.9rem;
+ white-space: normal;
+ color: black;
+ background: white;
}
-
+
/* Layout for meta timeline cards */
.time-meta{
- background-color: #f6faf6 !important;
- border-radius: 10px;
+ border-radius: 10px;
}
/* Tags */
.t-tag{
- box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
- color: #fff;
- font-size: 12px;
- font-weight: bold;
- letter-spacing: 1px;
- padding: 5px;
- margin-bottom: 10px;
- text-transform: uppercase;
- width: fit-content !important;
- }
-
- button.tabbutton.Patient.active, button.tabbutton.All.active,
- button.tabbutton.Industry.active, button.tabbutton.Academia.active,
- button.tabbutton.Medical.active, .modulators.active, .inhalations.active{
- border-color: black;
- }
+ box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
+ color: #fff;
+ font-size: 12px;
+ font-weight: bold;
+ letter-spacing: 1px;
+ padding: 5px;
+ margin-bottom: 10px;
+ text-transform: uppercase;
+ width: fit-content !important;
+}
+
+button.tabbutton.Patient.active, button.tabbutton.All.active,
+button.tabbutton.Industry.active, button.tabbutton.Academia.active,
+button.tabbutton.Medical.active, .modulators.active, .inhalations.active{
+ border-color: black;
+}
.colour-meta-tag{
- background-color: var(--igemlightgreen);
+background-color: var(--igemlightgreen);
}
/* and buttons */
button.tabbutton:nth-child(1){
- background-color: white;
- }
-
+ background-color: white;
+}
+
.Patient, button.tabbutton:nth-child(2){
- background-color: var(--accen-secondary);
- }
-
- .Medical, button.tabbutton:nth-child(3){
- background-color: var(--accent-primary);
- }
-
- .Academia, .Research, button.tabbutton:nth-child(4){
- background-color: var(--lightblue);
- }
-
- .Industry, button.tabbutton:nth-child(5){
- background-color: var(--mediumpurple);
- }
- .Activist, button.tabbutton:nth-child(6){
- background-color: var(--igemlightgreen);
- }
-
- .Ethics{
- background-color: var(--offblack);
- }
+ background-color: var(--accen-secondary);
+}
+
+.Medical, button.tabbutton:nth-child(3){
+ background-color: var(--accent-primary);
+}
+
+.Academia, .Research, button.tabbutton:nth-child(4){
+ background-color: var(--lightblue);
+}
+
+.Industry, button.tabbutton:nth-child(5){
+ background-color: var(--mediumpurple);
+}
+.Activist, button.tabbutton:nth-child(6){
+ background-color: var(--igemlightgreen);
+}
+
+.Ethics{
+ background-color: var(--offblack);
+}
+
-
/* * * * * * * */
/* TIMELINE BFH*/
/* * * * * * * */
/* Container */
.timeline-container {
- display: flex;
+ display: flex;
- flex-direction: column;
- position: relative;
- margin: 40px 0;
+ flex-direction: column;
+ position: relative;
+ margin: 40px 0;
}
/* Line */
.timeline-container::after {
- background-color: var(--text-primary);
- position: absolute;
- left: calc(50% - 2px);
- content: "";
- width: 4px;
- height: 100%;
- z-index: 0;
- }
-
+ background-color: var(--text-primary);
+ position: absolute;
+ left: calc(50% - 2px);
+ content: "";
+ width: 4px;
+ height: 100%;
+ z-index: 0;
+}
+
/* Cards */
.timeline-item {
- min-width: 100px;
- /* display: flex; */
- justify-content: flex-end;
- padding-right: 30px;
- position: relative;
- margin: 10px 0;
- width: 50%;
- }
- .timeline-item-content {
- box-shadow: 0 0 5px rgba(0, 0, 0, 0.3);
- border-radius: 5px;
- background-color: #fff;
- display: flex;
- flex-direction: column;
- align-items: flex-end;
- padding: 15px;
- position: relative;
- text-align: right;
- }
+ min-width: 100px;
+ /* display: flex; */
+ justify-content: flex-end;
+ padding-right: 30px;
+ position: relative;
+ margin: 10px 0;
+ width: 50%;
+}
+.timeline-item-content {
+ box-shadow: 0 0 5px rgba(0, 0, 0, 0.3);
+ border-radius: 5px;
+ background-color: #fff;
+ display: flex;
+ flex-direction: column;
+ align-items: flex-end;
+ padding: 15px;
+ position: relative;
+ text-align: right;
+}
/* Accomodate for alteration in card design */
.timeline-item:nth-child(odd) .timeline-item-content {
- text-align: left;
- align-items: flex-start;
- }
+ text-align: left;
+ align-items: flex-start;
+}
/* Tags */
.timeline-item-content .tag {
- color: #fff;
- font-size: 12px;
- font-weight: bold;
- top: 5px;
- left: 5px;
- letter-spacing: 1px;
- padding: 5px;
- margin-top: 5px;
- margin-left: 5px;
- position: absolute;
- text-transform: uppercase;
-}
- .timeline-item:nth-child(odd) .timeline-item-content .tag {
- left: auto;
- right: 5px;
- margin-right: 5px;
+ color: #fff;
+ font-size: 12px;
+ font-weight: bold;
+ top: 5px;
+ left: 5px;
+ letter-spacing: 1px;
+ padding: 5px;
+ margin-top: 5px;
+ margin-left: 5px;
+ position: absolute;
+ text-transform: uppercase;
+}
+ .timeline-item:nth-child(odd) .timeline-item-content .tag {
+ left: auto;
+ right: 5px;
+ margin-right: 5px;
}
/* Title design */
.timeline-item-content time {
- color: black;
- font-size: 16px;
- font-weight: bold;
- }
-
+ color: black;
+ font-size: 16px;
+ font-weight: bold;
+}
+
/* To create alternation */
.timeline-item:nth-child(odd) {
- align-self: flex-end;
- justify-content: flex-start;
- padding-left: 30px;
- padding-right: 0;
- }
+ align-self: flex-end;
+ justify-content: flex-start;
+ padding-left: 30px;
+ padding-right: 0;
+}
/* To create bigger first and final cards */
.timeline-end{
@@ -296,13 +295,13 @@ margin-bottom: 8vw;
/* Make short description on card bigger */
.timeline-item-content span{
- font-size: 18px;
- }
+ font-size: 18px;
+}
/* Make links on Cards fat */
- .timeline-item-content a {
- font-weight: bold;
- }
-
+.timeline-item-content a {
+ font-weight: bold;
+}
+
/* Circle */
.timeline-item-content .circle {
background-color: #fff !important;
@@ -316,80 +315,110 @@ height: 20px;
z-index: 100;
}
.timeline-item:nth-child(odd) .timeline-item-content .circle {
- right: auto;
- left: -53px;
+ right: auto;
+ left: -53px;
}
-
-
-
-
-
-
-
-
-
-
-
-
-
+
+
+
+
+
+
+
+
+
+
+
+
+
/* Checken ob wir das echt brauchen */
/* .timeline ol li:not(:first-child) {
- margin-left: 14px;
- }
- .timeline-item-content::after {
- background-color: #fff;
- box-shadow: 1px -1px 1px rgba(0, 0, 0, 0.2);
- position: absolute;
- right: -7.5px;
- top: calc(50% - 7.5px);
- transform: rotate(45deg);
- width: 15px;
- height: 15px;
- }
- .timeline-item:nth-child(odd) .timeline-item-content::after {
- right: auto;
- left: -7.5px;
- box-shadow: -1px 1px 1px rgba(0, 0, 0, 0.2);
- }
- .timeline-item-content p {
- font-size: 16px;
- line-height: 24px;
- margin: 15px 0;
- }
- .timeline-item-content a::after {
- font-size: 12px;
- }
- .card {
- border-radius: 4px;
+ margin-left: 14px;
+}
+.timeline-item-content::after {
background-color: #fff;
- color: #333;
- padding: 10px;
- box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
- width: 100%;
- max-width: 560px;
-
+ box-shadow: 1px -1px 1px rgba(0, 0, 0, 0.2);
+ position: absolute;
+ right: -7.5px;
+ top: calc(50% - 7.5px);
+ transform: rotate(45deg);
+ width: 15px;
+ height: 15px;
+}
+.timeline-item:nth-child(odd) .timeline-item-content::after {
+ right: auto;
+ left: -7.5px;
+ box-shadow: -1px 1px 1px rgba(0, 0, 0, 0.2);
+}
+.timeline-item-content p {
+ font-size: 16px;
+ line-height: 24px;
+ margin: 15px 0;
+}
+.timeline-item-content a::after {
+ font-size: 12px;
+}
+.card {
+border-radius: 4px;
+background-color: #fff;
+color: #333;
+padding: 10px;
+box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2);
+width: 100%;
+max-width: 560px;
+
}
.date {
- background-color: var(--text-primary) !important;
- padding: 4px !important;
- color: #fff !important;
- border-radius: 4px !important;
- font-weight: 500;
- font-size: .85rem;
-}
- .date-col{
- position: relative;
- background-color: #fff ;
- padding: 10px;
- width: 10%;
- border-right: #000;
- border-right-width: 2px;
-}
- .imageAtom{
- object-fit: cover;
- overflow: hidden;
- width: 100%;
- max-height: 400px;
+background-color: var(--text-primary) !important;
+padding: 4px !important;
+color: #fff !important;
+border-radius: 4px !important;
+font-weight: 500;
+font-size: .85rem;
+}
+.date-col{
+position: relative;
+ background-color: #fff ;
+ padding: 10px;
+ width: 10%;
+ border-right: #000;
+ border-right-width: 2px;
+}
+ .imageAtom{
+object-fit: cover;
+overflow: hidden;
+width: 100%;
+max-height: 400px;
}
- */
\ No newline at end of file
+*/
+.hpbuttonrow {
+ display: flex; /* Flex-Layout für die untere Reihe */
+ margin-top: auto; /* Schiebt diese Reihe nach unten */
+ align-items: center; /* Vertikale Zentrierung */
+}
+
+.fillup {
+flex: 1;
+display: flex; /* Flex-Layout aktivieren */
+align-items: center; /* Vertikale Zentrierung */
+justify-content: center; /* Horizontale Zentrierung */
+}
+
+.timeline-item .row:first-child {
+ flex: 1; /* Füllt den verbleibenden Raum aus */
+ display: flex; /* Flex-Layout aktivieren */
+ align-items: center; /* Vertikale Zentrierung */
+}
+
+/* Untere Reihe */
+.timeline-item .row:last-child {
+ margin-top: auto; /* Schiebt die letzte Reihe nach unten */
+}
+
+
+
+
+.fillup-wrapper{
+display: flex;
+}
\ No newline at end of file
diff --git a/src/App/mediarules.css b/src/App/mediarules.css
index 3f9a6506c4a69e154e4d6283d1a76a25797a7d53..6102f1d972ae5c0eca9b7d9c95a75a812fc64ff3 100644
--- a/src/App/mediarules.css
+++ b/src/App/mediarules.css
@@ -34,7 +34,9 @@
.col-6 {
width: 100%; /* Full width on tablets */
}
-
+ .progress-bar{
+ display: none !important;
+ }
}
/*For Smartphones*/
diff --git a/src/components/BFH-Timeline.tsx b/src/components/BFH-Timeline.tsx
index c422283cedfe10de81ec8dfea8d055135883cefb..bb431075796bae558f62d535a7dde3fc6ddac79f 100644
--- a/src/components/BFH-Timeline.tsx
+++ b/src/components/BFH-Timeline.tsx
@@ -387,8 +387,14 @@ export function BFHTimeline () {
<div id="multimedia" style={{display: "none"}}>
<p>Michael Gröning, who has many years of experience in a range of multimedia disciplines, including 3D animation, video and cinematography, film and audio production, post-production, voiceover and media design, held the practical workshop on multimedia. Firstly, the significance of the Promotion Video was elucidated, and the paramount importance of the general external representation was clarified. Questions and tricks provided the participants a basis for finding ideas for their videos, which were combined with story and mood boards and the reasonable use of AI.</p>
+ <div className="col">
+ <img src="https://static.igem.wiki/teams/5247/photos/meetup/workshop-multimedia-exposure-triangle.webp"/>
+ </div>
<p>A wide-ranging overview of various camera shots, lighting techniques and transitions was presented to the participants, equipping them with a useful toolkit for the production of cinematographic videos. Illustrative graphics, such as the Exposure Triangle, helped them to experiment with professional camera settings on their mobile phones. Through the implementation of voice warm-up exercises, the workshop participants were able to gain insights into the preparation of voice-overs. An introduction to various microphones and audio editing software enabled them to learn how voice recording is converted to studio quality.</p>
<p>The participants were able to gain valuable practical insights into the world of multimedia and thus prepare themselves to produce breathtaking videos. </p>
+ <div className="col">
+ <img src="https://static.igem.wiki/teams/5247/photos/meetup/workshop-multimedia2.webp" />
+ </div>
</div>
</TimelineItemPic>
<PanelTimelineItem></PanelTimelineItem>
diff --git a/src/components/Buttons.tsx b/src/components/Buttons.tsx
index 9a5e9f5fc8942bfd27abb2f0ec9d4f83a7431f03..32105fadf18fd671c9165b8a3f13fa3d7769da5f 100644
--- a/src/components/Buttons.tsx
+++ b/src/components/Buttons.tsx
@@ -177,15 +177,44 @@ export function ButtonOne({text, open, openclass}: {text:string, open:string, op
)
}
- return(
- <div className="boxy-1">
- <span typeof="button" onClick={openFromOtherPage(open)}>
- <div className="btn-new btn-one">
- {text}
- </div></span>
- </div>
- )
+ else{
+ return(
+ <div className="boxy-1">
+ <span typeof="button" onClick={openFromOtherPage(open)}>
+ <div className="btn-new btn-one">
+ {text}
+ </div></span>
+ </div>
+ )
+ }
+}
+
+export function ButtonOneWithScroll({text, open, openclass, scrollId}: {text:string, scrollId: string, open:string, openclass?: string}){
+ const { goToPageWithTabAndScroll } = useNavigation();
+ if (openclass) {
+ return(
+ <div className="boxy-1">
+ <a onClick={() => goToPageWithTabAndScroll({ path: "", tabId: open, scrollToId: scrollId })}>
+ <div className="btn-new btn-one">
+ {text}
+ </div>
+ </a>
+ </div>
+ )
+ }
+ else{
+ return(
+ <div className="boxy-1">
+ <span typeof="button" onClick={openFromOtherPage(open)}>
+ <div className="btn-new btn-one">
+ {text}
+ </div></span>
+ </div>
+ )
+ }
}
+
+
export function ButtonOneEngineering({label, open, scrollToId}: {label:string, open:string, scrollToId: string}){
return(
<div className="boxy-1">
diff --git a/src/components/Graph.tsx b/src/components/Graph.tsx
index 8a931c5881223ce86670d668c25e8b40d3d35ddb..8b7345a730dee60148b218d9bff4c541e03a4a8f 100644
--- a/src/components/Graph.tsx
+++ b/src/components/Graph.tsx
@@ -1,9 +1,37 @@
-import React from 'react';
import { Pie } from 'react-chartjs-2';
-import { Chart as ChartJS, ArcElement, Tooltip, Legend } from 'chart.js';
+import React from 'react';
+import { Bar } from 'react-chartjs-2';
+import { Chart as ChartJS, Tooltip, Legend,ArcElement, BarElement, CategoryScale, LinearScale, Title, RadialLinearScale } from 'chart.js';
+
+const backgroundcolorscale = [
+ 'rgba(133, 15, 120, 0.2)',
+ 'rgba(160, 167, 243, 0.2)',
+ 'rgba(245, 125, 34, 0.2)',
+ 'rgba(244, 204, 30, 0.2)',
+ 'rgba(130, 149, 164, 0.2)',
+ 'rgba(0, 101, 48, 0.2)',
+ 'rbga(184, 91, 209, 0.2)',
+ 'rbga(50, 35, 44, 0.2'
+]
-ChartJS.register(ArcElement, Tooltip, Legend);
+
+const bordercolorscale = [
+ 'rgba(133, 15, 120, 1)',
+ 'rgba(160, 167, 243, 1)',
+ 'rgba(245, 125, 34, 1)',
+ 'rgba(244, 204, 30, 1)',
+ 'rgba(130, 149, 164, 1)',
+ 'rgba(0, 101, 48, 1)',
+ 'rbga(184, 91, 209, 1)',
+ 'rbga(50, 35, 44, 1'
+]
+
+ChartJS.register(ArcElement, Tooltip, Legend, CategoryScale,
+ RadialLinearScale,
+ LinearScale,
+ BarElement,
+ Title);
const PieChart: React.FC = () => {
const data = {
@@ -18,29 +46,800 @@ const PieChart: React.FC = () => {
0.2384159999999995,
0.003703
],
- backgroundColor: [
- 'rgba(255, 99, 132, 0.2)',
- 'rgba(54, 162, 235, 0.2)',
- 'rgba(255, 206, 86, 0.2)',
- 'rgba(75, 192, 192, 0.2)',
- 'rgba(153, 102, 255, 0.2)',
- 'rgba(255, 159, 64, 0.2)',
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: '',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+
+
+export const OpenToGeneTherapyatients: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'Maybe', 'No'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 78.72,
+ 19.86,
+ 1.42
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Would you be open to gene therapy if it could significantly improve your symptoms?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+
+export const MostStressfulForRelativeatients: React.FC = () => {
+ const data = {
+ labels: ['Emotional Stress', 'Physiacal Symptoms', 'Financial Burden', 'Social Restrictions', 'Other'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 36.79,
+ 32.78,
+ 11.37,
+ 17.73,
+ 1.34
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Which aspects of the disease are most stressful for you or your relative?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const WhoAffectedatients: React.FC = () => {
+ const data = {
+ labels: ['I am affected', 'A Relative is affected'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 43.24,
+ 56.76
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Are you affected by cystic fibrosis yourself or are you related to someone with cystic fibrosis?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const DoYouWantMoreInfoatients: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'No'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 93.48,
+ 6.52
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Would you like to see more information on the subject of gene therapy?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const HowOftenTreatmentatients: React.FC = () => {
+ const labels = ['Rarely', 'Monthly', 'Weekly', 'Several times per week', 'Daily'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ label: "",
+ data: [
+ 6.49,
+ 6.49,
+ 15.59,
+ 9.73,
+ 62.7
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'How often do you or your relative need medical treatment or therapy?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const WhatCocernsAboutGeneTherapyatients: React.FC = () => {
+ const labels = ['Mo concerns', 'Ethical questions', 'Long-term effects', 'Safety and side effects', 'Cost and accessibility'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 0.54,
+ 10.18,
+ 59.46,
+ 59.46,
+ 32.43
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'What concerns do you have about gene therapy?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const HowMuchDoesItAffectYouatients: React.FC = () => {
+ const labels = ['1', '2', '3', '4', '5'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 4.32,
+ 12.43,
+ 42.16,
+ 32.97,
+ 8.11
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: "How much does cystic fibrosis affect your or your relative's daily life? (1 = Not at all, 5 = Very much)"
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+
+export const WhichTherapyDoYouUseatients: React.FC = () => {
+ const labels = ['Psychological therapy', 'Physical therapy', 'Nutritional therapy', 'Medication therapy', 'Inhalation therapy', 'Others'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 5.94,
+ 26.32,
+ 10.53,
+ 29.2,
+ 26.83,
+ 1.19
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'Which form(s) of therapy do you or your relative use?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const WhichSymptomsatients: React.FC = () => {
+ const labels = ['Other', 'Headache', "Delayed Growth", 'Underweight', 'Frequent lung infections', 'Muscle tremors/weakness', 'constipation', 'Abdominal pain', 'Chronic cough' ];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 4.99,
+ 6.98,
+ 6.23,
+ 13.47,
+ 13.72,
+ 2.0,
+ 10.47,
+ 23.19,
+ 18.95
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'Which symptoms do you or your relative have most frequently?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+
+export const BasicPositionatients: React.FC = () => {
+ const labels = ['1', '2', '3', '4', '5'];
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 2.14,
+ 5.17,
+ 27.14,
+ 30.00,
+ 35.00
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'What is your basic position on gene therapy? (1=Very negative, 5=Very positive)',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const AgeDiagnosisatients: React.FC = () => {
+ const labels = ['>20', '10-20', '1-10', 'first months', 'first week', 'Newborn Screening', 'Before birth'];
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 3.83,
+ 2.73,
+ 26.23,
+ 21.86,
+ 18.03,
+ 26.23,
+ 1.09
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'At what age were you or your relative diagnosed with cystic fibrosis?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const HeadrofGeneTherapyPatients: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'No'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 76.76,
+ 23.24
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Have you ever heard of gene therapy?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const MoreInfoOnTherapyBoth: React.FC = () => {
+ const labels = ['Yes', 'No'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ label: 'Affected',
+ data: [
+ 93.48,
+ 6.52
+
+ ],
+ backgroundColor: 'rgba(133, 15, 120, 0.2)',
+ borderColor: 'rgba(133, 15, 120, 1',
+ },
+ {
+ label: 'Unaffected',
+ data: [
+ 92.00,
+ 8.00
+ ],
+ backgroundColor: 'rgba(160, 167, 243, 0.2)',
+ borderColor: 'rgba(160, 167, 243, 1)',
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'Would you like to see more information on the subject of gene therapy?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+
+export const HeardOfCFPublic: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'No'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 82.89,
+ 17.11
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Have you heard of cystic fibrosis?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+
+export const HeadOfGeneTherapyPublic: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'No'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 67.58,
+ 32.42
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Have you ever heard of gene therapy?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+
+export const HowDidYouLearnPublic: React.FC = () => {
+ const labels = ['I am affected', 'Family/Friends', 'School/University', 'Media', 'Healthcare provider', 'Other'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ data: [
+ 1.23,
+ 25.15,
+ 20.86,
+ 44.17,
+ 3.68,
+ 4.91
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'How did you mainly learn about cystic fibrosis? ',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const HowWellDoYouUnderstandGFPublic: React.FC = () => {
+ const data = {
+ labels: ['Extremely well', 'Somewhat well', 'Not so well', 'Not at all'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 19.38,
+ 24.81,
+ 44.96,
+ 10.85
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'How well do you understand what gene therapy is?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const HowWellInformedAboutCFPublic: React.FC = () => {
+ const data = {
+ labels: ['Extremely well', 'Somewhat well', 'Not so well', 'Not at all'],
+ datasets: [
+ {
+ label: 'Percentage',
+ data: [
+ 6.37,
+ 21.66,
+ 58.60,
+ 13.38
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'How well informed are you about cystic fibrosis?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+export const WhatCouldGeneTherapyMeanForMedicinePublic: React.FC = () => {
+ const data = {
+ labels: ['Major advances in the treatment of diseases', 'Some progress, but also risks', 'More risks than benefits', 'No opinion'],
+ datasets: [
+ {
+ data: [
+ 49.59,
+ 47.97,
+ 1.63,
+ 0.81
],
- borderColor: [
- 'rgba(255, 99, 132, 1)',
- 'rgba(54, 162, 235, 1)',
- 'rgba(255, 206, 86, 1)',
- 'rgba(75, 192, 192, 1)',
- 'rgba(153, 102, 255, 1)',
- 'rgba(255, 159, 64, 1)',
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ borderWidth: 1,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'What do you think gene therapy could mean for medicine?',
+ },
+ };
+
+ return (
+ <div className="pie-chart-container">
+ <Pie data={data} options={options} />
+ </div>
+ );
+};
+
+
+export const WhatMeasuresPublic: React.FC = () => {
+ const labels = ['Publicity campaigns on TV, radio and social media', 'Information events in schools and communities', "Information materials in doctors' surgeries and hospitals", 'Organization of fundraising runs and charity events', 'Online platforms and forums for affected and interested parties', 'Cooperation with companies for awareness-raising initiatives', 'Integration of the topic into school lessons', 'Documentaries and short films about life with cystic fibrosis'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ label: 'General Survey',
+ data: [
+ 22.87,
+ 13.20,
+ 13.69,
+ 7.09,
+ 12.72,
+ 6.60,
+ 9.82,
+ 14.01
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'What measures do you think could be taken to raise awareness of cystic fibrosis?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+
+export const WouldYouDoGeneTherapyPublic: React.FC = () => {
+ const data = {
+ labels: ['Yes', 'No', 'Maybe'],
+ datasets: [
+ {
+ label: 'General Survey',
+ data: [
+ 85.22,
+ 13.04,
+ 1.74
],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
borderWidth: 1,
},
],
};
const options = {
responsive: true,
- maintainAspectRatio: false
+ maintainAspectRatio: false,
+ title: {
+ display: true,
+ text: 'Would you opt for gene therapy yourself?',
+ },
};
return (
@@ -50,4 +849,88 @@ const PieChart: React.FC = () => {
);
};
+
+export const WhatCocernsAboutGeneTherapyPublic: React.FC = () => {
+ const labels = ['No concerns', 'Ethical questions', 'Long-term effects', 'Safety and side effects', 'Cost and accessibility'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ label: 'General Survey',
+ data: [
+ 4.57,
+ 14.61,
+ 27.85,
+ 28.77,
+ 24.20
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'What concerns do you have about gene therapy?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
+export const WhatFormMoreInfoPublic: React.FC = () => {
+ const labels = ['Informations brochures', 'Websites and online resources', 'TV documentaries and programs', 'Lectures and seminars', 'School and university courses ', 'Consultations with doctors and specialists', 'Social media and online communities', 'Other'];
+
+ const data = {
+ labels,
+ datasets: [
+ {
+ label: 'General Survey',
+ data: [
+ 15.74,
+ 16.63,
+ 22.62,
+ 1.77,
+ 13.30,
+ 13.97,
+ 15.96,
+ 0
+ ],
+ backgroundColor: backgroundcolorscale,
+ borderColor: bordercolorscale,
+ },
+ ],
+ };
+ const options = {
+ responsive: true,
+ plugins: {
+ legend: {
+ position: 'top' as const,
+ },
+ title: {
+ display: true,
+ text: 'In what form would you like to see more information?',
+ },
+ },
+ };
+
+ return (
+ <div className="bar-chart-container">
+ <Bar options={options} data={data} />
+ </div>
+ );
+};
+
export default PieChart;
diff --git a/src/components/HeaderBox.tsx b/src/components/HeaderBox.tsx
index e30869a0291c826d730df326df7ab04fe09df45c..d80ebe95a4c336e99cd8d4166f0db6c6660f49db 100644
--- a/src/components/HeaderBox.tsx
+++ b/src/components/HeaderBox.tsx
@@ -13,7 +13,7 @@ export default function HeaderBox({children, title, title2}: Props ){
}
return(
<>
- <div className="row">
+ <div className="col">
<div className="col header-container">
<div className="row header-title">
<Hwave text={title}></Hwave>
diff --git a/src/components/HorizontalTimeline.tsx b/src/components/HorizontalTimeline.tsx
index 7cd76f97cc6f02cb9b1606aa58c86b570e1ad290..ec334623ca67c86a9907e59056ac76ea4c0a5797 100644
--- a/src/components/HorizontalTimeline.tsx
+++ b/src/components/HorizontalTimeline.tsx
@@ -10,15 +10,17 @@ function TimeItem({tag, title, pic, author, tabid}: ItemProps){
{tag}
</div>
- <div className="row align-items-center">
- <div className="col" >
- <img className="img-round" src={pic}/>
- </div>
- <div className="col" >
- {title}
+ <div className="fillup-wrapper">
+ <div className="row align-items-center fillup">
+ <div className="col" >
+ <img className="img-round" src={pic} />
+ </div>
+ <div className="col" >
+ {title}
+ </div>
</div>
- </div>
- <div className="row align-items-center">
+ </div>
+ <div className="row align-items-center hpbuttonrow">
<div className="col">
<p style={{marginTop: "10px"}}>{author}</p>
</div>
@@ -45,15 +47,17 @@ function TimeItem({tag, title, pic, author, tabid}: ItemProps){
{tag}
</div>
- <div className="row align-items-center">
- <div className="col" >
- <img className="img-cube" src={pic} />
- </div>
- <div className="col" >
- {title}
+ <div className="fillup-wrapper">
+ <div className="row align-items-center fillup">
+ <div className="col" >
+ <img className="img-cube" src={pic} />
+ </div>
+ <div className="col" >
+ {title}
+ </div>
</div>
- </div>
- <div className="row align-items-center">
+ </div>
+ <div className="row align-items-center hpbuttonrow">
<div className="col">
<p style={{marginTop: "10px"}}>{author}</p>
</div>
diff --git a/src/components/Loremipsum.tsx b/src/components/Loremipsum.tsx
index d5f43c6be71b5c647ac66e2f0a96c25443c94869..22a7b1dba31af0a1cd0207b75fc67c9b5a853cc5 100644
--- a/src/components/Loremipsum.tsx
+++ b/src/components/Loremipsum.tsx
@@ -1,6 +1,6 @@
export function LoremMedium(){
return(
- <>
+ <p className="lorem">
Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet. Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet. Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet.
Duis autem vel eum iriure dolor in hendrerit in vulputate velit esse molestie consequat, vel illum dolore eu feugiat nulla facilisis at vero eros et accumsan et iusto odio dignissim qui blandit praesent luptatum zzril delenit augue duis dolore te feugait nulla facilisi. Lorem ipsum dolor sit amet, consectetuer adipiscing elit, sed diam nonummy nibh euismod tincidunt ut laoreet dolore magna aliquam erat volutpat.
@@ -8,14 +8,14 @@ Duis autem vel eum iriure dolor in hendrerit in vulputate velit esse molestie co
Ut wisi enim ad minim veniam, quis nostrud exerci tation ullamcorper suscipit lobortis nisl ut aliquip ex ea commodo consequat. Duis autem vel eum iriure dolor in hendrerit in vulputate velit esse molestie consequat, vel illum dolore eu feugiat nulla facilisis at vero eros et accumsan et iusto odio dignissim qui blandit praesent luptatum zzril delenit augue duis dolore te feugait nulla facilisi.
Nam liber tempor cum soluta nobis eleifend option congue nihil imperdiet doming id quod mazim placerat facer
-</>
+</p>
)
}
export function LoremShort(){
return(
- <>
+ <p className="lorem">
Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet. Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et justo duo dolores et ea rebum. Stet clita kasd gubergren, no sea takimata sanctus est Lorem ipsum dolor sit amet.
- </>
+ </p>
)
}
\ No newline at end of file
diff --git a/src/components/Tabs.tsx b/src/components/Tabs.tsx
index 4c52c8d176090f9397d5aacb06bd620167140399..2327c157f1d6a3d3fe075708587751536c6ade8a 100644
--- a/src/components/Tabs.tsx
+++ b/src/components/Tabs.tsx
@@ -40,6 +40,12 @@ import Collapsible from "./Collapsible";
problem = true;
problem_desc.push("interview language");
}
+
+ /* Expert on */
+ let expert = "";
+ if (data[i].experton) {
+ expert = `Expert on ${data[i].experton}`;
+ }
/* Aim/Goal */
var goalheading: string = "";
@@ -152,19 +158,35 @@ import Collapsible from "./Collapsible";
<div className="row">
<div className="col-6">
<div className={"t-tag " + data[i].tag}>
- {data[i].job}
+ {data[i].job} {data[i].affiliation}
</div>
</div>
- <div className="col-3">{lang}</div>
+ <div className="col" style={{padding: "5px"}}>{expert}</div>
+ <div className="col" style={{width: "20%", flex: "1 0 0%", padding: "5px"}}>{lang}</div>
</div>
- <div className="row">
+ <div className="row align-items-stretch">
+ <div className="col d-flex flex-column">
+ <div className="row flex-grow-1 mitte">
+ <p style={{paddingTop: "50px", fontSize: "large"}}>Summary:</p>
+ <p>{data[i].summary}</p>
+ </div>
+ <div className="row unten" style={{fontSize: "large"}}>
+ See how this influenced our project at
+ </div>
+ </div>
+ <div className="col-3">
+ <img className="middle sechpro img-fluid" src={data[i].pictureurl} />
+ </div>
+ </div>
+ {/* <div className="row">
<div className="col">
- <BlockQuoteB text={data[i].quote} cite={quoted}></BlockQuoteB>
+ <p style={{paddingTop: "50px", fontSize: "large"}}>Summary:</p>
+ <p>{data[i].summary}</p>
</div>
<div className="col-3">
<img className="middle sechpro" src={data[i].pictureurl}/>
</div>
- </div>
+ </div> */}
<h4>{goalheading}</h4>
<div className="flexbox">
@@ -189,6 +211,9 @@ import Collapsible from "./Collapsible";
{imp_img}
</div>
+ <div className="col">
+ <BlockQuoteB text={data[i].quote} cite={quoted}></BlockQuoteB>
+ </div>
{int}
{refs}
</>
diff --git a/src/contents/Human Practices/Feedback.tsx b/src/contents/Human Practices/Feedback.tsx
new file mode 100644
index 0000000000000000000000000000000000000000..428064944556eabd27d34a9b0994bf3c500142ff
--- /dev/null
+++ b/src/contents/Human Practices/Feedback.tsx
@@ -0,0 +1,210 @@
+
+import * as Graph from '../../components/Graph';
+import { H4 } from '../../components/Headings';
+import { Collapsible } from "../../components/Collapsible";
+
+export function HPFeedback(){
+
+ return(
+ <div>
+ <H4 text="Our surveys on cystic fibrosis and gene therapy"></H4>
+ <p> We are proud of our surveys on gene therapy and cystic fibrosis (CF), which explore knowledge about the disease and willingness to embrace gene therapy as a potential treatment. Since we wanted to differentiate between the general public and affected CF patients, we created two different surveys.</p>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.HowOftenTreatmentatients/>
+ </div>
+ <div className="col">
+ <Graph.OpenToGeneTherapyatients/>
+ </div>
+ <div className="col">
+ <Graph.MoreInfoOnTherapyBoth/>
+ </div>
+ </div>
+ <div className="row ">
+ <div className="col">
+
+ <p>The majority of respondents (62.70%) indicated that they or their relative require medical treatment or therapy daily. Weekly treatment was necessary for 14.59%, while 9.73% needed therapy several times per week. Only 6.49% reported needing treatment either monthly or rarely. The high frequency of daily treatments highlights the heavy burden of managing cystic fibrosis and reinforces the potential appeal of gene therapy, which could reduce the need for constant medical intervention. </p>
+ </div>
+ <div className="col">
+ <p>A significant majority, 78.72%, indicated that they would be open to gene therapy if it significantly improved symptoms, while only 1.42% said no. This overwhelming support aligns with the hope patients have for less invasive and more effective treatments. This also reflects the possibility of gene therapy becoming a central treatment method, especially given the heavy therapeutic load CF patients already carry.</p>
+ </div>
+ <div className="col">
+
+ <p>A vast majority, 93.48%, expressed interest in more information about gene therapy. This mirrors the general public’s desire for further education and suggests that while there is strong support for gene therapy, people still feel they lack sufficient knowledge to make fully informed decisions. Patients especially emphasized the importance of safety and long-term efficacy, areas that should be focal points in future communications. </p>
+ </div>
+ </div>
+ <div>
+ <H4 text="Concluding thoughts "></H4>
+ <p>The surveys with both the general public and CF patients show promising openness towards gene therapy, though concerns about safety and long-term effects remain. Emotional stress was highlighted as a greater burden than physical symptoms, reinforcing the appeal of gene therapy to reduce both physical and emotional challenges. Most patients require daily or frequent therapies like medication, physiotherapy, and inhalation, making a less frequent or even one-time gene therapy, as proposed in our research, highly attractive. Participants added comments such as <strong>“The dream of healing still exists!â€</strong>, encouraging us in our research.</p>
+ <p>Both groups are ready for gene therapy, with patients showing fewer "no concerns," likely due to their familiarity with risks and off-target effects. This underscores the importance of our focus on safety and precision to minimize risks. Our research is designed to address these concerns through targeted approaches – <strong>we are PreCyse!</strong></p>
+ <p>Additionally, there’s a clear demand for more information, especially via platforms like TV, social media, and the internet. Targeted educational campaigns through these channels will be crucial to increase awareness and understanding, helping to build on the existing optimism and foster greater acceptance of gene therapy, like we do in our various public outreach efforts for science communication.</p>
+ </div>
+ <div>
+ <Collapsible id="collapsible1" open={false} title="See the full results of our surveys">
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.WhoAffectedatients/>
+ </div>
+ <div className="col">
+ <Graph.HeardOfCFPublic/>
+ </div>
+ <div className="col">
+ <Graph.HowDidYouLearnPublic/>
+ </div>
+ </div>
+ <div className="row">
+ <div className="col">
+ <p>56.76% of respondents reported that they are related to someone with CF, while 43.24% stated they are affected by CF themselves. This likely reflects the fact that many parents completed the survey on behalf of their children, as CF is typically diagnosed at a young age. The high involvement of parents underscores how the disease impacts not just the patients themselves but also their families, who are deeply involved in the day-to-day management of CF. This highlights the importance of considering both the perspectives of young patients and their families when discussing gene therapy and CF treatments, as parents often play a critical role in decision-making regarding new treatment options.</p>
+ </div>
+ <div className="col">
+ <p>82.89% of respondents have heard of cystic fibrosis, while 17.11% had not. The high level of awareness about CF suggests that the general public is relatively informed about the condition, possibly due to the visibility of the disease through media, health campaigns, or personal connections to affected individuals. However, the 17% unfamiliar with CF indicates that further outreach is necessary, particularly focusing on this demographic to spread knowledge about the disease and potential treatments, including gene therapy. </p>
+ </div>
+ <div className="col">
+ <p>The majority of respondents (44.17%) learned about CF through media channels, such as television, news, or the internet. Other significant sources of information include family and friends (25.15%), as well as educational institutions (20.86%). Interestingly, only 3.68% of respondents learned about CF from healthcare providers, suggesting that the disease is more commonly understood through external sources rather than direct medical education. This reliance on media and personal connections highlights the importance of accurate and accessible information in the public domain, especially when considering the introduction of gene therapy as a treatment option. </p>
+ </div>
+ </div>
+
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.AgeDiagnosisatients/>
+ <p>26.23% of respondents indicated that CF was diagnosed either through newborn screening or between the ages of 1 and 10. Another 21.86% reported diagnosis a few months after birth, and 18.03% were diagnosed about one week after birth. This highlights the early detection of CF, often requiring lifelong management, which can be emotionally challenging for families. Early diagnosis increases the appeal of treatments like gene therapy, which could offer long-term benefits with fewer interventions.</p>
+ </div>
+ <div className="col">
+ <Graph.HowMuchDoesItAffectYouatients/>
+ <p>42.16% of respondents rated the impact of cystic fibrosis on daily life as a 3 out of 5, indicating a moderate effect. Additionally, 32.97% rated the impact as a 2, while 12.43% rated it as a 4. Only 4.32% of respondents felt that CF had a very strong impact (rating it a 5), and 8.11% rated it a 1, suggesting little to no daily effect. These results indicate that for many patients and families, CF has a notable but varied impact on daily life, reinforcing the importance of treatments like gene therapy that could alleviate the burden. </p>
+ </div>
+ <div className="col">
+ <Graph.WhichSymptomsatients/>
+ <p>This chart shows that 23.19% of respondents identified abdominal pain as the most frequent symptom, followed by chronic cough (18.95%) and frequent lung infections (13.72%). Interestingly, symptoms like muscle weakness (2%) and delayed growth (6.23%) were less commonly reported. The emphasis on chronic respiratory and gastrointestinal symptoms aligns with CF being a metabolic disease affecting the whole body like experts such as Dr. Olariu explained to us, reinforcing the need for comprehensive treatments like gene therapy that target multiple aspects of the disease at the cellular level.</p>
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.WhichTherapyDoYouUseatients/>
+ <p>The most common therapies used by respondents included medication (29.20%), physiotherapy (26.32%), and inhalation therapy (26.63%). These treatments are prominently represented in CF care, but they also reflect a burdensome regimen that requires constant management. The frequency with which patients must undergo these treatments may increase their interest in gene therapy, which could offer a less demanding option with potentially longer-lasting results</p>
+ </div>
+ <div className="col">
+ <Graph.MostStressfulForRelativeatients/>
+ <p>The survey reveals that 36.79% of respondents identified emotional stress as the most stressful aspect of cystic fibrosis, closely followed by physical symptoms at 32.78%. Social restrictions were noted by 17.73% of respondents, and financial burden was a concern for 11.37%. Only 1.34% cited other factors. These results show that emotional and physical challenges dominate the stressors for patients and families, highlighting the need for treatments like gene therapy that could reduce both the physical and emotional burdens of managing CF. </p>
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.HeadrofGeneTherapyPatients/>
+ <p>Among this group, 76.76% of respondents had heard of gene therapy, which is a higher awareness rate than seen in the general public survey. However, 23.24% remain unfamiliar with it, pointing to a need for further education. The higher familiarity here could be attributed to the fact that patients and their families are more engaged with medical advancements due to the severe nature of CF. </p>
+ </div>
+ <div className="col">
+ <Graph.HeadOfGeneTherapyPublic/>
+ <p>When asked about gene therapy, 67.58% of respondents indicated familiarity with the concept, while 32.42% had not heard of it. This demonstrates a moderate level of awareness, but it is clear that a third of the population remains unaware of gene therapy. This gap in knowledge represents a significant opportunity for educational efforts, as the lack of familiarity could impact the acceptance and support for gene therapy as a viable treatment option for CF. The comments suggest that many see gene therapy as an emerging field, but there is some confusion regarding its practical applications.</p>
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.HowWellInformedAboutCFPublic/>
+ <p>In terms of knowledge about CF, 58.60% of respondents stated that they are somewhat well informed, and only 21.66% felt extremely well informed (see diagram 2). A smaller portion, 13.38%, indicated that they are not very informed, and 6.37% admitted to being not informed at all. This suggests that while CF is recognized by a large portion of the public, deeper knowledge about the disease is lacking. That is why we are doing science communication at our various public outreach events! </p>
+ </div>
+ <div className="col">
+ <Graph.WhatMeasuresPublic/>
+ <p>Respondents were asked what actions could be taken to improve CF awareness (see diagram 4). The most popular option, chosen by 22.87%, was publicity campaigns on TV, radio, and other mass media outlets. Information events at schools and universities followed at 13.20%, along with documentary films and short movies about life with CF (14.01%). These findings suggest that the public sees media as the most effective way to spread awareness, a strategy that could also be employed to educate about gene therapy. The public appears to favor visual and accessible formats, which could be used to highlight the benefits of new treatments like gene therapy. </p>
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.BasicPositionatients/>
+ <p>The survey reveals that 35.00% of respondents had a very positive view of gene therapy, and 30.00% rated it a 4 out of 5 (see diagram 20). Only 5.71% rated it a 2 or lower. The overall positivity suggests that many patients and families are hopeful about the potential of gene therapy, perhaps because of their familiarity with the limitations of current treatments. This optimism could be leveraged to support future clinical trials or educational initiatives.</p>
+ </div>
+ <div className="col">
+ <Graph.WhatCocernsAboutGeneTherapyatients/>
+ <p>Concerns about gene therapy primarily revolved around safety and side effects and long-term effects (both 59.46%) (see diagram 22). Cost and accessibility also remain important issues for 32.43% of respondents. Only 0.54% expressed no concerns, showing that while there is optimism, there are significant fears to address. These concerns were similarly expressed in the general public survey but are more pronounced among patients, likely due to their firsthand experience with long-term treatments.</p>
+ </div>
+ <div className="col">
+ <Graph.WhatCocernsAboutGeneTherapyPublic/>
+ <p>The most common concern, shared by 28.77% of respondents, was related to the safety and side effects of gene therapy, followed by long-term effects (27.85%) and costs or accessibility (24.20%) (see diagram 9). Ethical questions were raised by 14.61% of participants, while only 4.57% had no concerns at all. These concerns echo comments made in other parts of the survey, where respondents expressed interest in learning more about the safety protocols and regulatory measures surrounding gene therapy. Clearly, addressing these concerns in future public engagements will be critical to fostering wider acceptance. </p>
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ <div className="col">
+
+ </div>
+ </div>
+ <div className="row align-items-center">
+ <div className="col">
+ <Graph.WhatCouldGeneTherapyMeanForMedicinePublic/>
+ <p>Nearly half (49.59%) of respondents believe that gene therapy represents a major advance in the treatment of diseases, while 47.97% acknowledged that gene therapy offers some progress but also carries risks (see diagram 7). Less than 2% of respondents expressed concern that gene therapy could bring more risks than benefits. This overall positive outlook on gene therapy is encouraging, but it also underscores the need to address concerns about safety and long-term effects, which were often mentioned in the comments. The optimism shown here can be a strong foundation for promoting gene therapy, especially with appropriate education on mitigating risks.</p>
+ </div>
+ <div className="col">
+ <Graph.WouldYouDoGeneTherapyPublic/>
+ <p>A strong majority, 85.22% of respondents, indicated that they would consider opting for gene therapy, with only 1.74% saying they would not, and 13.04% responding with "maybe." (see diagram 8). This result demonstrates considerable openness to gene therapy among the public, though the minority expressing hesitation suggests there are lingering doubts. Comments frequently mentioned concerns over safety and long-term effects, suggesting that these issues need to be addressed to convert "maybe" responses into more confident support for gene therapy.</p>
+ </div>
+ <div className="col">
+ <Graph.WhatFormMoreInfoPublic/>
+ <p>When asked how they would prefer to receive more information, 22.62% of respondents selected TV documentaries and programs as their preferred medium, while 16.63% expressed interest in websites and online resources (see diagram 11). This preference for visual and online formats aligns with the public’s general reliance on media for learning about CF and other medical topics. Social media and online communities (15.96%) also ranked highly, indicating that digital platforms are an effective way to reach a broad audience. These findings can guide future efforts to create engaging and informative content about CF and gene therapy.</p>
+ </div>
+
+ </div>
+ </Collapsible>
+ </div>
+ </div>
+ )
+}
\ No newline at end of file
diff --git a/src/contents/Human Practices/Further Engagement/Education.tsx b/src/contents/Human Practices/Further Engagement/Education.tsx
index 1dbd250a1f6832cd0a9219f0389cbfbfaafd6605..219e2ed2f64342a70ca8f837d5388ef1f7e69f48 100644
--- a/src/contents/Human Practices/Further Engagement/Education.tsx
+++ b/src/contents/Human Practices/Further Engagement/Education.tsx
@@ -1,6 +1,7 @@
-import { ButtonOne } from "../../../components/Buttons";
+import { ButtonOneWithScroll } from "../../../components/Buttons";
import { H4 } from "../../../components/Headings";
import { H5 } from "../../../components/Headings"
+import { TabScrollLink } from "../../../components/Link";
export function HPEducation(){
@@ -8,21 +9,66 @@ export function HPEducation(){
<div className="col">
<div className="row align-items-center" style={{marginTop: "5vh", marginBottom: "5vh"}}>
<div className="col">
- <ButtonOne openclass="edu-cycletab" text="Overview" open="edu-overview"></ButtonOne>
+ <ButtonOneWithScroll openclass="edu-cycletab" text="Overview" open="edu-overview" scrollId="edu-heading"/>
</div>
<div className="col">
- <ButtonOne openclass="edu-cycletab" text="Teuto ruft!" open="teutoruft"></ButtonOne>
+ <ButtonOneWithScroll openclass="edu-cycletab" text="Teuto ruft!" open="teutoruft" scrollId="teuroruft-heading"/>
</div>
<div className="col">
- <ButtonOne openclass="edu-cycletab" text="Schüler*innen Akademie" open="akademie"></ButtonOne>
+ <ButtonOneWithScroll openclass="edu-cycletab" text="Schüler*innen Akademie" open="akademie" scrollId="student-academy-heading"/>
</div>
+ <div className="col">
+ <ButtonOneWithScroll openclass="edu-cycletab" text="MINT Sommer" open="mint" scrollId="mint-heading"/>
+ </div>
+ </div>
+
+
+
+
+
<div id="edu-overview" className="edu-cycletab" style={{display: "block"}}>
- <H4 id="edu-heading" text="Our education and outreach"/>
- <p>Education and outreach remain vital, even without being a special prize focus. They help us share knowledge, inspire people, and create lasting impact. By making information accessible, we empower the public to make informed decisions and engage in meaningful discussions.</p>
- <p></p>
- <H4 id="edu-why-heading" text="If not as a special prize - then why?"/>
- <p>Human-centered design is essential for our Integrated Human Practices, ensuring that our project is aligned with the real needs and concerns of the people it aims to serve. Outreach and education are key components of this approach, as they allow us to communicate our goals and inform the public about both our project and the critical issue of cystic fibrosis (CF). By engaging with diverse audiences—patients, families, schools, and the wider community—we raise awareness about CF, while fostering a deeper understanding of the challenges involved. This feedback-driven interaction not only builds trust but also helps us refine our work to have a meaningful impact on those affected by CF. Through educational programs, workshops, and outreach initiatives, we aim to bridge the gap between scientific research and the public, ensuring that our project is both accessible and impactful.</p>
- <p></p>
+ <H4 id="edu-heading" text="If not as a special prize - then why?"/>
+ <p>While education is not directly considered part of Human Practices in iGEM, it remains a vital component of synthetic biology and scientific advancement
+ for several important reasons:</p>
+ <ul>
+ <li>To help people make <b>informed choices</b> and encourage <b>emancipation through education</b>.</li>
+ <li>Only informed participants allow for <b>ethical engagement</b>.</li>
+ <li>To ensure <b>continuous learning</b> in order to secure the future of synthetic biology and cystic fibrosis research.</li>
+ <li>Only awareness and knowledge can <b>prevent misuse and misinformation</b>.</li>
+ </ul>
+ <p>This is applicable to both cystic fibrosis and synthetic biology in general.</p>
+ <p>Many people gravitate towards fields they are interested in. Awareness, exploration, and receiving new knowledge are necessary to cultivate an authentic
+ interest, which, together with positive social interaction, forms a promising foundation for a lasting interest<TabScrollLink tab="edu-overview" num="1" scrollId="desc-edu"/>. As future researchers and part of a
+ competition aiming for continuous innovation, we feel education is an important ascpect that should not be shrugged off under the guise of focusing on Human Practices.</p>
+
+ <H4 id="edu-why-heading" text="Our educational activities"/>
+ <p>In both "Der Teuto ruft!" and the CeBiTec Student Academy, our team focused on education through personal contact not only as way to spread
+ awareness about cystic fibrosis, but to spread the love we have for what we do. </p>
+ <p>We are glad to have had the possibility to work with such different audiences. While "Der Teuto ruft!" had a focus on families and required a creative
+ approach, the "Schüler*innen Akademie" and "MINT Sommer" allowed us to interact with aspiring researchers who may very well be our future classmates at
+ Bielefeld University.
+ </p>
+ <p>However, we came to realize that "Der Teuto ruft!" may have been the more impactful event for our personal growth. It took us out of the familiar
+ "science bubble" and into a space where we could interact with the general public—people who don’t necessarily have a scientific background. This
+ experience reminded us how non-scientists perceive complex topics like gene therapy and cystic fibrosis. It also highlighted the importance of not only
+ ethical responsibility but also social responsibility in communicating science. We gained and regained insight into the concerns, misconceptions, and
+ hopes that the public has regarding synthetic biology, allowing us to better understand what is not only scientifically sound but also socially
+ acceptable. We are confident participating in "Der Teuto ruft!" very positively influenced our approach to further communication. </p>
+ <H4 text="References"></H4>
+ <ol>{/*<!-- Citation num 1--> */}
+ <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-edu">
+ <span property="schema:author" typeof="schema:Person">
+ <span property="schema:Name"> Aswegen, E.</span>
+ <span property="schema:Name"> Pendergast, D.</span>
+ </span>
+ <span property="schema:name"> The impact of interest: an emergent model of interest development in the early years</span>.
+ <i property="schema:publisher" typeof="schema:Organization"> Early Child Development and Care</i>
+ <b property="issueNumber" typeof="PublicationIssue"> 193</b>
+ , <span property="schema:pageBegin"> 1</span>-<span property="schema:pageEnd">15</span>
+ (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
+ <a className="doi" href="https://doi.org/10.1080/03004430.2023.2245575"> doi: 10.1080/03004430.2023.2245575</a>
+ </li>
+ </ol>
</div>
<div id="akademie" className="edu-cycletab" style={{display: "none"}}>
@@ -53,10 +99,11 @@ Due to our collaboration with the Student Academy, we conducted the nanopore seq
One such experiment involved creating a lung model from balloons and straws, demonstrating the difficulty patients have in breathing by having the children blow into the straws. Additionally, we set up a tank with a mixture of starch and water to simulate mucus and placed a ball on top. The children tried to blow the ball across the surface, illustrating how hard it is for air to move through mucus compared to water, where the ball moved much more easily.
The very little ones could paint coloring pages which we designed and printed for them. For the adults, we provided information about our project and discussed the implications and potential of gene therapy for cystic fibrosis. These conversations made it abundantly clear that degrees of knowledge on this topic widely vary throughout the public and we were happy to fill in the existing gaps in people's knowledge and exchange points of view on gene therapy.
Moreover, we connected with other institutions and participants at the event. We shared our booth at Bielefeld’s “Skulpturenpark†on the outside with <a href="https://bts-ev.de/bielefeld/" title="btS" > btS </a>, the life science student initiative from Bielefeld University, with whose members we had stimulating discussions as well. We were more than delighted when the city of Bielefeld featured us on their Instagram, highlighting our presence during "Der Teuto ruft!". This collaboration helped us reach a wider audience and raise awareness about our research efforts.</p>
-<p></p>
-<a href="https://unibielefeldde.sharepoint.com/sites/iGEM2024teams/_layouts/15/stream.aspx?id=%2Fsites%2FiGEM2024teams%2FFreigegebene%20Dokumente%2FGeneral%2FFotos%2C%20Videos%20und%20Co%2FTeuto%20ruft%2FVideo%20Insta%20Teuto%20Ruft%2Emov&ga=1&referrer=StreamWebApp%2EWeb&referrerScenario=AddressBarCopied%2Eview%2Ee4a43a55%2Dfff3%2D4b44%2Db081%2Dad26306f93e0" title="video Teuto ruft" > watch me</a>
-<p></p>
-<H5 id="conclusion? " text="What is our conclusion"/>
+<br/>
+{/* <a href="https://unibielefeldde.sharepoint.com/sites/iGEM2024teams/_layouts/15/stream.aspx?id=%2Fsites%2FiGEM2024teams%2FFreigegebene%20Dokumente%2FGeneral%2FFotos%2C%20Videos%20und%20Co%2FTeuto%20ruft%2FVideo%20Insta%20Teuto%20Ruft%2Emov&ga=1&referrer=StreamWebApp%2EWeb&referrerScenario=AddressBarCopied%2Eview%2Ee4a43a55%2Dfff3%2D4b44%2Db081%2Dad26306f93e0" title="video Teuto ruft" > watch me</a>
+ */}
+ <br/>
+<H5 id="conclusion" text="What is our conclusion"/>
<p>Despite the changeable weather, we could educate many people of Bielefeld's community about cystic fibrosis, our therapeutic approach and gene therapy in general and had the opportunity to improve our science communication for the future as well so it was a successful event! </p>
<div className="row align-items-center">
@@ -67,8 +114,30 @@ Moreover, we connected with other institutions and participants at the event. We
<img src="https://static.igem.wiki/teams/5247/photos/edcation-and-outreach/teutoruft-gruppe.jpeg"></img>
</div>
</div>
+
</div>
- </div>
+
+
+
+
+ <div id="mint" className="edu-cycletab" style={{display: "none"}}>
+ <H4 id="mint-heading" text="MINT Sommer"/>
+ <H5 id="what and why mint summer" text="What is MINT Summer and why were we participating?"/>
+ <div className="row">
+ <img src="https://static.igem.wiki/teams/5247/photos/hp/mintsommerlogo.png" style={{width:"30%", height:"20%"}}/>
+ <div className="col">
+ <p>“MINT Summer 2024†is a comprehensive program designed primarily for high school graduates of the class of 2024, who are considering pursuing studies in STEM fields (Science, Technology, Engineering, and Mathematics, including teaching degrees). The program is perfect for those who are still uncertain if they want to study in STEM or which specific discipline aligns best with their interests.</p>
+ <p>Our participation in <a href="https://www.uni-bielefeld.de/studium/studieninteressierte/mint-sommer/" title="Mint Summer" >MINT Summer </a> offered us the chance to raise awareness of cystic fibrosis and showcase our cutting-edge approach to develop an optimized gene therapy to combat this disease. Through the event we engaged with potential future scientists and researchers, informing them about our project, iGEM and the importance of scientific research in advancing medical treatments. This program not only allows us to share our mission but also to inspire the next generation of STEM students by highlighting the real-world impact of their studies. </p>
+ </div>
+ </div>
+ <H5 id="strategy summer" text="What was our strategy?"/>
+ <p>Our objective at MINT Summer was to inform attendees, especially aspiring STEM students, about the unique challenges faced by cystic fibrosis (CF) patients, with a particular focus on lung-related complications. We drew heavily on the insights gained from the Science Communication Workshop at the BFH Meetup, which provided us with the perfect framework to meticulously plan our outreach for this event. This foundation allowed us to craft engaging and educational activities that effectively conveyed the complexities of CF to our audience, ensuring our message was both impactful and accessible. </p>
+ <p>We took the opportunity to explain the iGEM competition and our project to participants. We shared how iGEM is a global competition that brings together student teams to solve real-world problems using synthetic biology. We discussed how our approach aims to correct the genetic mutation responsible for CF, potentially offering a more effective treatment. By engaging with attendees, we were able to highlight the significance of our research and the impact it could have on improving the lives of those affected by this challenging condition. They got the opportunity to contribute to our project by participating in our survey. </p>
+ <p>Over the time of two weeks, we established meaningful connections with professors, students, and participants across various STEM fields during the event, like the student initiative btS and the Campusbrauerei Bielefeld. Sharing our project with the life science students was helpful, motivating and opened the door to engaging discussions that enriched our perspective and fostered collaboration. These interactions allowed us to connect with experts and students from different disciplines, enhancing our understanding of how our gene therapy research for cystic fibrosis fits within the broader scientific landscape.</p>
+ <H5 id="conclusion summer" text="What is our conclusion?"/>
+ <p>The experience allowed us to refine our science communication skills and connect with a broad range of STEM professionals and students. Overall, the event was a valuable opportunity for both education and professional growth, making it a rewarding and impactful experience for our team. </p>
+ </div>
+
</div>
);
}
\ No newline at end of file
diff --git a/src/contents/Human Practices/Further Engagement/Entrepreneurship.tsx b/src/contents/Human Practices/Further Engagement/Entrepreneurship.tsx
index 5e30c2e06f8e57e44123152354d3b9353390162d..972865712d37118d6dcd9b8ea50addb6f32184e0 100644
--- a/src/contents/Human Practices/Further Engagement/Entrepreneurship.tsx
+++ b/src/contents/Human Practices/Further Engagement/Entrepreneurship.tsx
@@ -1,5 +1,6 @@
-import { ButtonOne } from "../../../components/Buttons";
-import { H4 } from "../../../components/Headings";
+import { ButtonOneWithScroll } from "../../../components/Buttons";
+import { H4, H5 } from "../../../components/Headings";
+import { LoremShort } from "../../../components/Loremipsum";
export function HPEntrepreneur(){
@@ -8,27 +9,218 @@ export function HPEntrepreneur(){
<div className="col">
<div className="row align-items-center" style={{marginTop: "5vh", marginBottom: "5vh"}}>
<div className="col">
- <ButtonOne openclass="ent-cycletab" text="Overview" open="ent-overview"></ButtonOne>
+ <ButtonOneWithScroll openclass="ent-cycletab" text="Overview" open="ent-overview" scrollId="ent-heading"/>
</div>
<div className="col">
- <ButtonOne openclass="ent-interview" text="GxP" open="ent-interview"></ButtonOne>
+ <ButtonOneWithScroll openclass="ent-interview" text="Interviews with Founders" open="ent-interview" scrollId="ent-inter-heading"/>
+ </div>
+ <div className="col">
+ <ButtonOneWithScroll openclass="ent-interview" text="Next Steps" open="ent-next" scrollId="ent-course-heading"/>
</div>
</div>
<div id="ent-overview" className="ent-interview" style={{display: "block"}}>
- <H4 id="ent-heading" text="Entrepreneurship"/>
- <p> It helps us transform innovative ideas into real-world solutions, drive change, and create long-lasting impact. By building sustainable business models and engaging with stakeholders, we empower communities to benefit from our work and enable broader adoption of our solutions.</p>
- <p></p>
- <H4 id="ent-why-heading" text="If not as a special prize - then why?"/>
- <p>Human-centered design is also at the heart of our entrepreneurial efforts, ensuring that our innovations directly address the real needs of the people we aim to serve. Entrepreneurship is a key component of this process, as it allows us to not only develop effective solutions but also bring them to market in a meaningful way. By interacting with patients, families, healthcare professionals, and the broader community, we refine our product based on their input and the specific challenges they face, such as those associated with cystic fibrosis (CF). This approach builds trust, fosters collaboration, and ensures that our solutions can reach those who need them most. Through entrepreneurial initiatives, business strategies, and partnerships, we aim to create sustainable and scalable impact, bridging the gap between scientific innovation and everyday life.</p>
- <p></p>
+ <H4 id="ent-heading" text="If not as a special prize, then why?"/>
+ <p>Entrepreneurship is not only an interesting possibility but necessary to turn our ideas and results into a real product that can help people. </p>
+ <p>THat is why in this section, we focus on the aspects of entrepreneurship that are crucial for the potential successful realisation of our project to develop new therapies for cystic fibrosis. A pivotal moment was our interview with Nicole Friedlein, which gave us valuable insights into the challenges and opportunities in the field of biomedical innovation. The discussions in the interview encouraged us to look more closely at the regulatory requirements, which is why one team member completed a GxP course and subsequently trained the team in this area. In addition, we conducted further interviews in the area of entrepreneurship to gain a better understanding of the practical aspects of business development. These experiences not only enriched the scientific depth of our project, but also sharpened our perspective on the practical implementation and market launch of new therapies.
+ </p>
+ <H4 id="ent-heading" text="Our Entrepreneurship"/>
+ <LoremShort/>
</div>
+
<div id="ent-interview" className="ent-interview" style={{display: "none"}}>
- <H4 id="ent-course-heading" text="GxP course"/>
+ <H4 id="ent-inter-heading" text="Question 1: Idea Validation"/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">How did you test the marketability of your scientific idea - how did you get a first impression that there is a need for your product or service? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory tested the marketability of their idea through participation in scientific conferences. Engaging with other scientists and presenting their own research allowed them to gauge the interest and needs within the field. Direct feedback from these events helped them assess whether their product was aligned with market demand and if they needed to modify or accelerate certain aspects of development.
+ </p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale validated their idea by seeking feedback from both the scientific community and industry professionals at conferences and networking events. They noticed growing interest in RNA therapeutics, particularly for lung delivery. The challenges surrounding delivery systems, especially highlighted during the COVID-19 pandemic, confirmed that there was a strong market demand for their technology, which motivated them to move forward with commercialization.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>For our project, a concrete next step would be to actively seek feedback from cystic fibrosis research communities and biotech conferences. We should continue to present our RNA-based gene therapy approach to experts in gene editing and delivery systems, specifically asking for input on our delivery mechanism using lipid nanoparticles (LNPs). This early engagement could help identify whether our approach addresses a real unmet need in cystic fibrosis treatment and refine our product to better meet clinical and patient needs.
+ </p>
+ <H4 id="ent-expert-heading" text="Question 2: Proof-of-Concept"/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">How did you develop the first proof-of-concept before you had investors? Did you work with universities or research institutions to get access to laboratories and equipment? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory was aware of the demand for DNA early on, as the founders had already produced DNA for customers during their previous work. Initially, they collaborated with academic partners and customers to meet the demand for plasmid DNA, which helped them establish a proof-of-concept. Over time, they shifted from primarily working with academic institutions to collaborating more with the research-based pharmaceutical industry, while maintaining their connections with universities. </p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale developed their proof-of-concept through collaborations with universities. They started with in vitro cell culture models and later advanced to more complex systems, such as air-liquid interface models and precision-cut lung slices. Additionally, they performed an in vivo study and had access to human lung tissue samples, which helped them validate their technology in a relevant clinical context before seeking investors. </p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>As the iGEM Team of Bielefeld University, we have access to excellent research infrastructure. A concrete next step for us could be leveraging the university's cell culture and gene editing facilities to develop an advanced proof-of-concept. Additionally, collaborating with other departments within Bielefeld or partner institutions could help us perform in vivo studies. This would allow us to validate our lipid nanoparticle delivery system and present strong preliminary data for future investors or partners. </p>
+
+ <H4 text="Question 3: Transition from Research to Commercialization "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">What were the biggest challenges in the transition from exploring a scientific idea to a commercial start-up? Looking back, are there certain steps you would have taken earlier or differently? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>One of the major challenges was ensuring that their idea was marketable, which is never entirely clear at the beginning. Another significant challenge was securing capital for development. They emphasized the importance of spending only what was available and highlighted the role of research funding programs (EU or national) in supporting early-stage biotech companies. Looking back, they might not have done things differently but emphasized the importance of careful financial planning and making sure the product has a potential market.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>For RNhale, the biggest challenge was securing sufficient funding, as transitioning from university-based research to the private sector requires a strategic approach to bridging this gap. They also mentioned that developing a clear business model earlier on could have sped up the process. Another challenge was forming partnerships with industry at an earlier stage, which might have eased both the funding process and commercialization efforts.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders emphasized the challenge of securing funding and building a clear business model. At Bielefeld University, we should consider exploring partnerships with industry early, such as biotech firms or pharmaceutical companies. A concrete next step could be identifying relevant funding programs like EXIST or EU grants, which could help bridge the gap between our university research and commercialization. Developing a business model tailored to RNA-based therapeutics for cystic fibrosis will also be critical to attract investors. </p>
+
+
+ <H4 text="Question 4: Funding "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">What sources of funding did you use in the early stages of your company? Were there any special funding programs or investors that specialized in biotechnology start-ups? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>In the early stages, funding programs for start-ups did not exist as they do today. PlasmidFactory relied on traditional sources like their local bank and creative solutions like purchasing second-hand equipment through platforms like eBay. Their first customers also played a key role, as the revenue from initial sales allowed them to reinvest in the business and further its growth.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale initially relied on public funding from university grants and government programs such as GrowBio and EXIST, which provided crucial pre-seed support. As they transitioned into a private company, they secured additional funding through the European Union’s EIC Transition grant. They also attracted venture capital from firms specializing in biotech, such as the Hightech-Gründerfonds and international investors like Karma Fund and Wellington, who understood the long timelines and high costs associated with biotech development.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders highlighted the importance of securing diverse funding sources early on. A concrete next step could be collaborating with the university’s startup support services to identify potential investors, especially those with biotech experience. Additionally, exploring non-traditional sources such as industry-sponsored research collaborations could provide crucial initial funding to support the development of our cystic fibrosis gene therapy. </p>
+
+ <H4 text="Question 5: Team Building "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">What qualifications and skills were particularly important when building your team? Did you bring in experts from industry or other areas? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>For PlasmidFactory, honesty, commitment, and hard work were crucial. The initial team consisted of lab technicians, biochemists, and biologists. Over time, they expanded to include employees from various fields, such as biotechnology and even non-scientific areas like business administration and marketing. Bringing in someone with industry experience was seen as particularly valuable, as industry operates differently from academic environments. </p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale emphasized the need for a balance between technical expertise and business acumen when building their team. They prioritized operational alignment and recruited individuals skilled in biologics manufacturing, in vitro and in vivo performance, and business development. They also brought in external experts, such as a patent attorney, regulatory advisors, and preclinical specialists. Many of these connections came from networking and startup bootcamps, which provided valuable resources for building a well-rounded team. </p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders stressed the importance of combining technical expertise with business acumen. At Bielefeld University, we should focus on building a diverse team that includes not only scientists skilled in RNA therapeutics and gene editing but also individuals with experience in business development and regulatory affairs. A concrete next step could be reaching out to the university’s business and legal faculties to bring in experts who can help us navigate commercialization and regulatory processes. </p>
+
+
+ <H4 text="Question 6: Regulatory Challenges "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">What regulatory challenges did you face in your start-up process, and how did you overcome them? What advice would you give to other start-ups in terms of compliance with regulations and laws? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory emphasized the strict regulations in the biotech and pharmaceutical industries, particularly in the field of genetic engineering. They highlighted the importance of adhering to laws from the start. Since the founders didn’t have extensive expertise in regulatory compliance, they overcame this challenge by collaborating with institutions like universities and research centers, which provided the necessary regulatory knowledge.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale faced significant regulatory challenges, particularly in meeting the strict requirements for clinical testing. They needed to conduct preclinical studies under Good Laboratory Practice (GLP) conditions and ensure their product was manufactured under Good Manufacturing Practice (GMP). To navigate these regulations, they worked with external advisors and contract research/manufacturing organizations (CROs and CMOs). They recommended integrating regulatory considerations early in the development process and maintaining close contact with regulatory experts and authorities to prevent delays and ensure compliance.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders highlighted the complexity of regulatory compliance, particularly in biotech. For our project, we need to integrate regulatory considerations early, especially regarding clinical trials and safety standards for gene therapies. A concrete step would be to consult with experts in Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP), ensuring that our lipid nanoparticle system meets the necessary regulations. Additionally, early engagement with regulatory bodies could smooth the path to eventual clinical trials. </p>
+
+ <H4 text="Question 7: Market Entry and Networking "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">What role did networks and partnerships play when you entered the market? How did you acquire your first customers or partners, and which strategies were particularly successful? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory's strategy was simple: demonstrate scientific expertise to build trust. This approach helped them gain credibility and attract customers. They emphasized patience, noting that success can take a long time—sometimes up to 10 years—but perseverance and maintaining strong relationships with partners and customers were key to their success.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>Networks and partnerships were critical for RNhale's market entry. They leveraged connections from their university affiliations, startup bootcamps, and conferences to build relationships with industry experts. Their first customers and partners were acquired through these networks. Participating in startup accelerators and pitch events allowed them to showcase their business model and technology, which helped secure partnerships and build credibility in the RNA therapeutics field.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders stressed the importance of building networks and partnerships early. For our project, we should focus on developing relationships with industry experts and potential partners through conferences, pitch events, and biotech startup programs. A concrete next step could be to participate in networking events where we can present our RNA-based therapy and gain valuable contacts in the pharmaceutical industry. This could also help us identify early customers or strategic partners to accelerate market entry. </p>
+
+
+ <H4 text="Question 8: Intellectual Property (IP) "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">How did you secure your intellectual property rights? What steps were necessary to obtain patents or licenses? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory highlighted the importance of keeping ideas confidential in the early stages to prevent others from taking them. They discussed three strategies: recording the idea as a deed with a notary, registering it as a utility model for lower-cost protection, and eventually pursuing a full patent, initially focusing on Germany and possibly a few other countries. In licensing agreements, they ensured that fees were only due to the technology owner once the startup earned money from it.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale secured their intellectual property through university licensing and strategic patent filings. Early work was patented by the university, and they secured exclusive rights to use the technology for commercialization through a licensing agreement. For later developments, they took a strategic approach, filing priority patents to protect novelty and expanding patent claims within the 12-month window to cover commercially relevant aspects. They emphasized the importance of negotiating IP agreements early, especially when working with universities, and planning a robust patent strategy.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders emphasized the importance of securing IP early, especially when working with universities or external partners. For our project, we should develop a clear patent strategy for our RNA-based cystic fibrosis therapy. A concrete next step would be to consult with IP experts to ensure our technology is well protected. Negotiating early IP agreements with the university or external collaborators is crucial to safeguard our innovations while allowing room for future developments. </p>
+
+ <H4 text="Question 9: Pivoting "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">Were there moments when you had to adapt or completely change your original idea? What were the triggers, and how did you deal with them? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory did not experience a major pivot in their business model but emphasized the importance of constant dialogue with customers. In some cases, customers did not initially accept their ideas, but rather than giving up, they remained patient and revisited the discussion with references from other satisfied clients to build credibility. </p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale had to adapt their original idea several times. One significant pivot was shifting from providing a service for lipid nanoparticle formulation to developing their own proprietary therapeutic product for severe asthma. Feedback from investors and participation in startup bootcamps revealed a stronger market demand for a product-driven approach with a clear exit strategy. This led them to revise their business model while still leveraging their core technology.</p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders discussed the importance of remaining adaptable to feedback and market needs. For our project, we must be open to making strategic adjustments based on the feedback we receive from clinical trials, investors, or partners. A concrete next step would be to establish a flexible business plan that allows for pivots, such as focusing on specific subtypes of cystic fibrosis patients or adjusting our lipid nanoparticle delivery system to meet evolving technological or regulatory requirements. </p>
+
+ <H4 text="Question 10: Long-term Vision "/>
+ <H5 text="What we asked the Founders"/>
+ <p className="ask-p">Did you have something like a long-term vision for your company and, if so, how did you reconcile this vision with the short-term goals? </p>
+ <H5 text="What the Founders had to say "/>
+ <p><b>PlasmidFactory (Martin Schleef)</b></p>
+ <p>PlasmidFactory had a long-term vision from the beginning, which was to produce pharmaceutical-grade plasmid DNA (GMP). However, the process of building and certifying a GMP facility was costly and time-consuming. To manage short-term goals, they developed an intermediate quality standard called “high quality,†which allowed them to supply starting materials for pharmaceutical vector production. It took them 25 years to open their first GMP facility, demonstrating their focus on long-term planning while balancing immediate milestones.</p>
+ <p><b>RNhale (Benjamin Winkeljann)</b></p>
+ <p>RNhale’s long-term vision was to develop RNA-based therapeutics, particularly for respiratory diseases. They reconciled this vision with short-term goals by breaking their vision into actionable milestones, such as developing a lead candidate for severe asthma. Alongside their core therapeutic focus, they offered small-scale manufacturing services to generate revenue and build credibility. This dual approach helped them maintain momentum while working towards their larger goal of establishing a pipeline of RNA therapeutics. </p>
+ <H5 text="Learnings and Implications for our project "/>
+ <p>Both founders highlighted the importance of aligning short-term goals with a long-term vision. For our project, we must ensure that while focusing on immediate milestones, such as demonstrating the efficacy of our RNA-based therapy, we maintain sight of our broader goal: revolutionizing cystic fibrosis treatment. A concrete next step would be to break down our long-term vision into actionable short-term goals, such as optimizing our delivery system and securing regulatory approvals, while building a sustainable pipeline for future RNA therapeutics. </p>
+ </div>
+
+
- <H4 id="ent-expert-heading" text="GxP Expert"/>
-
+ <div id="ent-next" className="ent-interview" style={{display: "none"}}>
+ <H4 id="ent-course-heading" text="GXP in the context of clinical trials "/>
+ <H5 text="Role of GXP in Scaling and Proof-of-Concept"/>
+ <p>To take our RNA-based gene therapy for cystic fibrosis closer to clinical trials and potential market entry, investors and regulatory authorities need
+ confidence in the quality and reliability of our work. While the current iGEM proof-of-concept demonstrates feasibility, investors typically expect a
+ more sophisticated validation, especially in <b>In-Vivo models</b>. GXP would be fundamental in achieving this next step: </p>
+ <ul>
+ <li><b>Good Laboratory Practice (GLP)</b> would guide the experimental setup in animal models, ensuring that the results we generate are reproducible and meet regulatory standards for data integrity and safety. This is critical for progressing to preclinical trials. </li>
+ <li><b>Good Manufacturing Practice (GMP) </b> would play a key role as we look to scale our production. Not only would we need to produce our RNA constructs consistently, but we would also have to demonstrate that our manufacturing process can be scaled while maintaining quality and safety, which is essential for attracting investment. </li>
+ </ul>
+ <H5 text="Insights from GXP Training"/>
+ <p>One of our team members recently completed an intensive GXP course, which reinforced the importance of standard operating procedures (SOPs) and rigorous documentation throughout the development process​(HP_GXP course). This training has prepared us to implement practices such as Failure Mode and Effects Analysis (FMEA), a risk assessment technique that will help identify potential issues early in the development phase, ensuring we can preemptively mitigate risks. </p>
+ <p>As we aim to move towards clinical trials, GXP ensures that our product development pipeline is both ethical and compliant with international safety standards, which will be key in discussions with investors and regulatory bodies. By embedding these principles early, we not only enhance the quality and reliability of our data but also lay a foundation for future clinical applications. </p>
+ <H5 text="Next Steps"/>
+ <p>As we move forward, our team plans to gradually integrate GXP standards into our development pipeline. The knowledge gained from the GXP course, along with expert consultations, provides us with a better understanding of the regulatory expectations in the biotechnology field. While we are still in the early stages of applying these standards, we aim to align our processes with industry requirements. This will ensure that, as we progress, we maintain a high level of quality and compliance, particularly as we scale up production and move closer to potential clinical applications. </p>
+ <H4 text="Market Evaluation"/>
+ <H5 text="1. Target Market Definition "/>
+ <p><b>Patient Population:</b> Cystic Fibrosis (CF) is a rare genetic disorder affecting over 80,000 individuals worldwide, with a significant
+ concentration in North America and Europe. About 90% of CF patients have at least one copy of the F508del mutation, which makes them potential
+ candidates for therapies targeting this mutation [1] [2]. </p>
+ <p><b>Geographical Focus:</b>The largest markets are in North America and Europe, where CF prevalence is highest, and access to advanced therapies
+ like RNA-based treatments is well-supported. This would be the primary focus for our therapy, particularly in countries with established CF
+ treatment infrastructures such as the U.S., Germany, and the U.K. [3].</p>
+ <p><b>Unmet Needs: </b>Despite advancements like CFTR modulators (e.g., Kaftrio), around 10% of patients do not respond to current treatments and rely on
+ symptomatic care [4]. Our RNA-based gene therapy could address this unmet need, specifically targeting the Delta F508 mutation for which many patients have
+ limited options. </p>
+ <H5 text="Market Size and Growth Potential"/>
+ <p><b>Market Size: </b> The global cystic fibrosis treatment market was valued at USD 9.41 billion in 2023 and is expected to grow to USD 29.19 billion by
+ 2032, with a compound annual growth rate (CAGR) of 13.4% [5]. This growth is driven by advancements in gene therapy and increased research funding. Gene
+ therapy targeting the F508del mutation, the most common CF mutation, presents a significant market opportunity within this larger CF treatment market[6]. </p>
+ <p><b>Growth Drivers:</b> The increase in CF patient lifespan due to improved treatments, alongside ongoing innovation in RNA-based therapies, offers
+ significant growth potential. The rise in government-backed initiatives and non-profit funding further supports market expansion [7][8]. </p>
+ <p><b>Opportunity for RNA-Based Therapies:</b> While current treatments like CFTR modulators provide relief for many patients, approximately 10% of CF
+ patients do not benefit from these therapies [9]. Our RNA-based therapy has the potential to capture this segment of the market, addressing an unmet
+ clinical need.</p>
+ <H5 text="3. Competitive Landscape "/>
+ <p><b>Current Competitors:</b>The cystic fibrosis treatment space is dominated by pharmaceutical giants such as Vertex Pharmaceuticals, which has developed
+ CFTR modulators like Kaftrio/Trikafta. These modulators are currently the gold standard for treating CF patients with the F508del mutation [10].
+ Other key players in the market include Novartis, Gilead Sciences, and AbbVie, all of whom are active in CF drug development[11].</p>
+ <p><b>Gene Therapy Competitors:</b>While CFTR modulators have been highly successful, several companies are exploring gene therapies aimed at addressing the
+ root cause of CF by correcting or replacing defective CFTR genes. Early-stage gene therapy trials have faced challenges, but advancements in delivery
+ technologies and CRISPR-based therapies are opening new pathways[12].</p>
+ <p><b>Our Differentiation: </b> Unlike existing CFTR modulators that require lifelong administration, our RNA-based therapy aims to provide a more
+ permanent solution by directly addressing the genetic cause of CF, specifically targeting patients who do not respond to current CFTR modulators.
+ This could position us as a unique player in the market, targeting an underserved patient group.</p>
+ <H5 text="4. Barriers to Entry "/>
+ <p><b>Regulatory Hurdles:</b>One of the biggest challenges in bringing a gene therapy to market is navigating the complex regulatory environment.
+ Compliance with Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) is essential for obtaining approvals from bodies like the FDA and EMA.
+ Securing approval for RNA-based gene therapies, particularly those targeting rare diseases like cystic fibrosis, can involve lengthy and expensive clinical
+ trials[13][14].</p>
+ <p><b>High R&D Costs:</b> Developing gene therapies involves significant upfront costs, from research and development to clinical trials. For a small
+ biotech startup, securing the necessary funding can be a barrier, especially when competing against established pharmaceutical companies with larger R&D
+ budgets[15].</p>
+ <p><b>Delivery Challenges:</b> Effective delivery of RNA-based therapies to the lungs remains a technical barrier. While lipid nanoparticles (LNPs) show
+ promise, optimizing the delivery method to ensure consistent, safe, and effective distribution of the therapy in lung tissues is a challenge that still
+ needs to be fully addressed [16].</p>
+ <p><b>Market Saturation and Entrenched Competitors:</b> The CF treatment market is already dominated by established players like Vertex Pharmaceuticals.
+ Gaining a foothold in a market where CFTR modulators are the standard of care will require demonstrating significant clinical advantages, particularly for
+ patients not served by existing treatments[17].</p>
+ <H5 text="5. Go-to-Market Strategy"/>
+ <p><b>Initial Focus on Clinical Partnerships:</b> The first step in bringing our RNA-based gene therapy to market will be partnering with academic
+ institutions and clinical research centers to conduct initial clinical trials. Establishing credibility through collaborations with key opinion leaders
+ in cystic fibrosis treatment will help build trust and validate the efficacy of our therapy [18][19].</p>
+ <p><b>Early Adopters: </b>Our focus will be on targeting early adopters, such as specialized cystic fibrosis clinics and hospitals that are familiar
+ with cutting-edge gene therapies. These institutions are more likely to adopt novel treatments and provide us with real-world data to further refine our
+ therapy[20].</p>
+ <p><b>Partnerships with Biotech and Pharmaceutical Companies:</b> Partnering with established biotech or pharmaceutical companies could help accelerate
+ commercialization by providing access to distribution channels, regulatory expertise, and additional funding. Licensing agreements or co-development
+ deals with companies specializing in gene therapy could be key to scaling production[21].</p>
+ <p><b>Regulatory Strategy:</b>Navigating the regulatory environment will be a priority, and early engagement with the FDA, EMA, and other regulatory
+ bodies will help ensure a smoother approval process. Focusing on orphan drug designation or fast-track approvals for rare diseases like cystic fibrosis
+ could expedite the regulatory timeline[22].</p>
+ <p><b>Long-Term Vision:</b> After initial success in treating cystic fibrosis, our RNA-based therapy could be expanded to treat other genetic disorders.
+ The modular nature of our technology allows us to adapt the therapy for other rare diseases, providing a broader market potential in the future[23].</p>
</div>
</div>
diff --git a/src/contents/Human Practices/Further Engagement/FurtherEngagement.tsx b/src/contents/Human Practices/Further Engagement/FurtherEngagement.tsx
index b7129c2cb84553e628de306dcf98f94bb5cfe301..fb80f18ef1859418d10ba38f4100e62d7d0026ab 100644
--- a/src/contents/Human Practices/Further Engagement/FurtherEngagement.tsx
+++ b/src/contents/Human Practices/Further Engagement/FurtherEngagement.tsx
@@ -9,12 +9,12 @@ export function HPFurtherEngagement(){
return(
<Section title="Further Engagement" id="Further Engagement">
- <Subesction title="Public Engagement" id="Further Engagement1">
- <HPOutreach/>
- </Subesction>
- <Subesction title="Education" id="Further Engagement2">
+ <Subesction title="Education" id="Further Engagement1">
<HPEducation/>
</Subesction>
+ <Subesction title="Public Engagement" id="Further Engagement2">
+ <HPOutreach/>
+ </Subesction>
<Subesction title="Entrepreneurship" id="Further Engagement3">
<HPEntrepreneur/>
</Subesction>
diff --git a/src/contents/Human Practices/Further Engagement/Outreach.tsx b/src/contents/Human Practices/Further Engagement/Outreach.tsx
index 9a16f2d2786daec1a82c451e19996b28c6822a39..de5ca8b529961cf505ebbcbdfcc81a323a79257a 100644
--- a/src/contents/Human Practices/Further Engagement/Outreach.tsx
+++ b/src/contents/Human Practices/Further Engagement/Outreach.tsx
@@ -1,6 +1,5 @@
import { ButtonOne } from "../../../components/Buttons";
import { H4 } from "../../../components/Headings";
-import { LoremMedium } from "../../../components/Loremipsum";
import { useNavigation } from "../../../utils/useNavigation";
export function HPOutreach(){
@@ -21,26 +20,38 @@ export function HPOutreach(){
<div id="out-overview" className="out-cycletab" style={{display: "block"}}>
- <H4 id="out-heading" text="Our education and outreach"/>
- <LoremMedium/>
<H4 id="out-why-heading" text="If not as a special prize - then why?"/>
- <LoremMedium/>
+ <p>While many of our efforts in science communication were educational, we also recognized the importance of public engagement through activities
+ that were not focused on formal education but rather on raising awareness. Initiatives like MUKOmove and our waffle sale were essential in bringing
+ cystic fibrosis (CF) into public focus and showing a visible commitment to the cause.</p>
+ <p>While being a superficial contact, publich enganegment and outreach serves as a reminder that science does not happen in isolation - it is rooted
+ in real-world problems that impact individuals and communities. Establishing presence allows diverting interest to our project and our cause which in turn
+ paves the way to edcuate interested people and laying the groundwork for a deeper connection between us and our project and the general public. </p>
+ <H4 id="out-heading" text="Our public engagement"/>
+ <p>Our public engagement served both as a form of spreading awareness and to establish first contacts. By inviting other people in Bielefeld to join our team
+ for MUKOmove, we were able to reach a wider audience and foster connections that extended beyond our university.</p>
+ <p>In addition to our in-person events, we used social media as a tool to keep the community engaged and updated. We shared our progress in
+ MUKOmove, promoted our events, and posted educational content about cystic fibrosis and gene therapy. Our social media presence helped us
+ stay connected with a broader audience, ensuring that even those who could not attend our events could still follow along and support our mission.</p>
+ <p>
+ Through these efforts, we also made valuable connections, resulting in an interview with the "Muko Dino" Thomas Malenke[Link]. This highlighted the power
+ of online platforms in expanding our reach and fostering collaboration beyond our immediate community.</p>
</div>
<div id="Waffle sale" className="out-cycletab" style={{display: "none"}}>
- <H4 id="Waffle sale" text="Waffle sale"/>
- <div className="row">
- <div className="full-small col3">
+ <div className="col">
+ <H4 text="Waffle Sale"></H4>
+ <div className="row">
+ <div className="col">
+ <p>To support our research project and raise funds for our iGEM team at Bielefeld University, we decided to organize a waffle sale in the main hall of the university. This initiative was aimed at raising awareness about our project and collecting funds for our research into cystic fibrosis. </p>
+ <p>The sale took place in cystic fibrosis awareness month May in the Great Hall of our University. As people passed by, we engaged them by introducing our research group and explaining our project’s objectives. We shared information about cystic fibrosis and why we are raising money. Our goal was to not only just to sell waffles, but also to educate the university community about our research and its’ potential impact. The response has been overwhelmingly positive. Many were genuinely interested in our work and asked for more details about our research and the goals of our project. This enthusiasm strengthened our commitment to the project and highlighted the importance of community involvement in scientific research. </p>
+ <p>The waffle sale was a great success, both in terms of raising funds and increasing awareness about our work within the university. It was a collaborative effort that brought our team closer together and demonstrated the power of community support in advancing scientific research. </p>
+ </div>
+ <div className="col-4">
+ <img src="https://static.igem.wiki/teams/5247/photos/edcation-and-outreach/screenshot-2024-09-25-202008.png" style={{objectFit: "cover", maxHeight: "50%", width: "100%"}}/>
</div>
</div>
- <div className="col">
- <h3>Waffle sale</h3>
- <p>To support our research project and raise funds for our iGEM team at Bielefeld University, we decided to organize a waffle sale in the main hall of the university. This initiative was aimed at raising awareness about our project and collecting funds for our research into cystic fibrosis. </p>
- <p>The sale took place in cystic fibrosis awareness month May in the Great Hall of our University. As people passed by, we engaged them by introducing our research group and explaining our project’s objectives. We shared information about cystic fibrosis and why we are raising money. Our goal was to not only just to sell waffles, but also to educate the university community about our research and its’ potential impact. The response has been overwhelmingly positive. Many were genuinely interested in our work and asked for more details about our research and the goals of our project. This enthusiasm strengthened our commitment to the project and highlighted the importance of community involvement in scientific research. </p>
- <p>The waffle sale was a great success, both in terms of raising funds and increasing awareness about our work within the university. It was a collaborative effort that brought our team closer together and demonstrated the power of community support in advancing scientific research. </p>
- <div className="col">
- <img src="https://static.igem.wiki/teams/5247/photos/edcation-and-outreach/screenshot-2024-09-25-202008.png" style={{width:"60%", height:"70%"}}/>
- </div>
+
</div>
</div>
@@ -64,12 +75,14 @@ export function HPOutreach(){
<div className="row">
<div className="col">
<h3>Why and in which ways were we invested in MUKOmove? </h3>
- <p>We did not stop at our participation itself – we wanted to make other people from our university and city
+ <p>While MUKOmove was not a scientific or educational event, it played an important role in demonstrating our presence in the broader CF
+ community.</p>
+ <p>We did not stop at our participation itself - we wanted to make other people from our university and city
aware of the event and collect sport hours for cystic fibrosis with them by inviting them to join our team.
Our survey about cystic fibrosis awareness and our discussions with <a onClick={() => goToPagesAndOpenTab('InvWesthoff', '/human-practices?tab=')}>Kathrin Westhoff</a>, the head of a
practice for physiotherapy in Gütersloh who is also treating young CF patients, showed us how little known
this illness still is. Especially the interview with the physiotherapist made us realize how important
- exercise is for everyone and how it brings a community together – we wanted to establish MUKOmove in
+ exercise is for everyone and how it brings a community together - we wanted to establish MUKOmove in
Bielefeld. That is why we really got the publicity going by putting up posters and distributing flyers
at the university and in our city as you can see in the following picture. </p>
</div>
@@ -82,11 +95,11 @@ export function HPOutreach(){
while the entire MUKOmove had a goal of collecting 24,000 sport hours. In cooperation with our university's
sports facilities, using their <a href="https://www.uni-bielefeld.de/einrichtungen/hochschulsport/zusatzangebote/houbi/">“HOUBI-Aktivmobil"</a> and other equipment, we organized a team event at the sports
ground of our university at the begin of MUKOmove. Everyone was warmly invited to our event on May 8th, and
- it was a lot of fun to play various sport games together outside in the sun – check out in the following
+ it was a lot of fun to play various sport games together outside in the sun - check out in the following
video! </p>
<div className="row align-items-center">
<div className="col">
- <img src="https://www.mapcom.com/wp-content/uploads/2015/07/video-placeholder.jpg"></img>
+ <iframe title="Bielefeld-CeBiTec: MUKOmove (2024) [English]" width="560" height="315" src="https://video.igem.org/videos/embed/dd3e6eff-95f5-47f4-a0fc-f416db88dfe4?autoplay=1" frameBorder="0" allowFullScreen={true} sandbox="allow-same-origin allow-scripts allow-popups allow-forms"></iframe>
</div>
</div>
<br/>
diff --git a/src/contents/Human Practices/Further Engagement/Partnerships.tsx b/src/contents/Human Practices/Further Engagement/Partnerships.tsx
index 253ef3e165421949f194bd84f0c9c684d5a00735..519cd0bdeffa1f8be4a6e0c3ba84ceb72eb36d09 100644
--- a/src/contents/Human Practices/Further Engagement/Partnerships.tsx
+++ b/src/contents/Human Practices/Further Engagement/Partnerships.tsx
@@ -1,12 +1,12 @@
import { H4 } from "../../../components/Headings";
-import { LoremMedium } from "../../../components/Loremipsum";
export function HPPartnerships(){
return(
<div className="col">
- <H4 text="Heading"></H4>
- <LoremMedium/>
+ <H4 text="CF Vests"></H4>
+ <p>CF Vests Worldwide is a dedicated charity organization committed to providing life-saving vest equipment to those in need, regardless of their financial situation. But they can't do it alone — they need your support. Help us make a difference! By donating to CFVWW, you can directly impact the lives of cystic fibrosis patients, giving them the chance to breathe easier and live fuller lives. Every contribution counts.</p>
+ <p><b>oin us in the fight against cystic fibrosis.</b>Donate today and help us bring hope, one vest at a time! Together, we can change lives.</p>
</div>
)
}
\ No newline at end of file
diff --git a/src/contents/Human Practices/IHP.tsx b/src/contents/Human Practices/IHP.tsx
index b52c4325db0251fefb74bfd03f7f7ed30ed51aed..fd0d0a1ea2ea5699a1ef3231800af8581d81d3d8 100644
--- a/src/contents/Human Practices/IHP.tsx
+++ b/src/contents/Human Practices/IHP.tsx
@@ -2,6 +2,7 @@ import { ButtonOne } from "../../components/Buttons";
import { HPTimeline } from "../../components/HP-timeline";
import { LoremMedium, LoremShort } from "../../components/Loremipsum";
import { Section, Subesction } from "../../components/sections";
+import { HPFeedback } from "./Feedback";
import { HP3new } from "./HP svgs/hp3";
import { HPUnderstanding } from "./HP svgs/understanding";
@@ -114,7 +115,7 @@ export function HPIntegrated(){
<LoremMedium/>
</Subesction>
<Subesction title="Feedback" id="Integrated Human Practices4">
- <LoremMedium/>
+ <HPFeedback/>
</Subesction>
<Subesction title="Conclusion" id="Integrated Human Practices5">
<LoremMedium/>
diff --git a/src/contents/Human Practices/Introduction.tsx b/src/contents/Human Practices/Introduction.tsx
index e8b479e725ab6b8c1d0be9636d73520571e6208f..8321f26772f441d18e814e532e6f5ba63320717f 100644
--- a/src/contents/Human Practices/Introduction.tsx
+++ b/src/contents/Human Practices/Introduction.tsx
@@ -7,6 +7,7 @@ export function HPIntroduction(){
return(
<Section title="Introduction" id="Introduction">
+
<div className="row align-items-center" style={{marginTop: "5vh", marginBottom: "1vh"}}>
<div className="col">
<ButtonOne openclass="intro-cycletab" text="Our Understanding of HP" open="understanding"></ButtonOne>
@@ -18,6 +19,7 @@ export function HPIntroduction(){
<ButtonOne openclass="intro-cycletab" text="Our Target Groups" open="targets"></ButtonOne>
</div>
</div>
+ <br/>
<div className="col intro-cycletab" id="understanding" style={{display: "block"}}> understanding <LoremMedium/> </div>
<div className="col intro-cycletab" id="mission" style={{display: "none"}}>mission <LoremMedium/> </div>
<div className="col intro-cycletab" id="targets" style={{display: "none"}}>targets <LoremMedium/> </div>
diff --git a/src/contents/description.tsx b/src/contents/description.tsx
index 71f65bb142f07756a9c82c2d3676711962cb7b4c..4233c408daad267befdad951983079262a1651df 100644
--- a/src/contents/description.tsx
+++ b/src/contents/description.tsx
@@ -22,10 +22,10 @@ export function Description() {
<div className="row mt-4">
<div className="col">
<Section title="Abstract" id="Abstract">
- <p id="obenindescription" >We are proud to introduce our next-generation prime editing technology <PreCyse/> . We aim to develop an innovative gene therapy against cystic fibrosis, tackling the most common mutation ΔF508 of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We optimize lipid nanoparticles (LNPs) for the efficient and cell-specific delivery of our therapeutic mRNA. Current treatment strategies are limited in terms of speed, precision and effectiveness, often failing to achieve long-lasting improvements. In addition, high costs and limited accessibility of pharmaceuticals contribute to adverse prognosis of many patients. We want to develop a monthly applied which represents a cure that is more advanced and user-friendly compared to other medications due to its longer lasting time, lowering the frequency of use. </p>
+ <p id="obenindescription" >We are proud to introduce our next-generation prime editing technology <PreCyse/> . We aim to develop an innovative gene therapy against cystic fibrosis, tackling the most common mutation F508del of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We optimize lipid nanoparticles (LNPs) for the efficient and cell-specific delivery of our therapeutic mRNA. Current treatment strategies are limited in terms of speed, precision and effectiveness, often failing to achieve long-lasting improvements. In addition, high costs and limited accessibility of pharmaceuticals contribute to adverse prognosis of many patients. We want to develop a monthly applied which represents a cure that is more advanced and user-friendly compared to other medications due to its longer lasting time, lowering the frequency of use. </p>
</Section>
<Section title="Our Motivation" id="Our Motivation">
- <p>We chose to focus on CF and specifically the ΔF508 mutation due to its prevalence and the severe impact it has on patients' lives. Additionally, our team includes members who have close friends affected by this condition, giving us a personal connection and a strong motivation to find a solution. By targeting the ΔF508 mutation, we aim to develop a therapy that could potentially, not only benefit many CF patients and make a significant improvement in their lives, but also can serve as a template, which research groups can use to target other genetic diseases. </p>
+ <p>We chose to focus on CF and specifically the F508del mutation due to its prevalence and the severe impact it has on patients' lives. Additionally, our team includes members who have close friends affected by this condition, giving us a personal connection and a strong motivation to find a solution. By targeting the F508del mutation, we aim to develop a therapy that could potentially, not only benefit many CF patients and make a significant improvement in their lives, but also can serve as a template, which research groups can use to target other genetic diseases. </p>
<div className="row align-items-center">
<div className="col" >
</div>
@@ -41,7 +41,7 @@ export function Description() {
<div className="col">
<p data-aos="zoom-y-out" >Cystic fibrosis (CF) is the most common life-limiting genetic disorder in the Caucasian population. In Europe, CF affecting about 1 in 3,000 newborns
<SupScrollLink label="1"/>.</p>
- <p> It is caused by mutations in the CFTR gene, which controls ions and water movement in cells. This leads to thick mucus, clogging airways, and frequent infections. The defective CFTR protein impacts the respiratory and digestive systems, causing chronic lung infections, breathing difficulties, and malnutrition. CF's severity varies, but it reduces life quality and expectancy. There are over 1,700 CFTR mutations; the ΔF508 mutation is most common, present in 70% of cases. It prevents proper protein folding, affecting its function. </p>
+ <p> It is caused by mutations in the CFTR gene, which controls ions and water movement in cells. This leads to thick mucus, clogging airways, and frequent infections. The defective CFTR protein impacts the respiratory and digestive systems, causing chronic lung infections, breathing difficulties, and malnutrition. CF's severity varies, but it reduces life quality and expectancy. There are over 1,700 CFTR mutations; the F508del mutation is most common, present in 70% of cases. It prevents proper protein folding, affecting its function. </p>
<Collapsible id="fanzorcas-collapsible" title="Cas vs. Fanzor">
<p>The mutations can be divided into six classes [9]:</p>
<p>Class I mutations prevent the synthesis of CFTR proteins altogether, meaning no channels are produced.</p>
@@ -73,20 +73,34 @@ export function Description() {
</Subesction>
<Subesction title="The CFTR Protein" id="Cystic Fibrosis2">
- <div className="rowalign-items-center">
- <div className="full-small col-2">
- <img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/>
+ <div className="row align-items-center">
+ <figure>
+ <div className="row">
+ <div className="col">
+ <img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/>
+ </div>
+ <div className="col">
<img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/>
</div>
+ </div>
+ <figcaption><b>Figure x.</b> </figcaption>
+ </figure>
+
<div className="col">
<p>Text about CFTR <LoremMedium/></p>
- <div className="col gif-wrapper">
- <img className="fanzor gif" src="https://static.igem.wiki/teams/5247/fanzor/cftr-wt.gif"></img>
- </div>
+ <div className="figure-wrapper">
+ <figure>
+ <div className="col gif-wrapper">
+ <img className="fanzor gif" src="https://static.igem.wiki/teams/5247/fanzor/cftr-wt.gif"></img>
+ </div>
+ <figcaption> <b>Figure 3.</b>Phase contrast image of HEK293T at 20x magnification</figcaption>
+ </figure>
+ </div>
+
</div>
</div>
</Subesction>
- <Subesction title="ΔF508" id="Cystic Fibrosis3">
+ <Subesction title="F508del" id="Cystic Fibrosis3">
<p>A multitude of mutations in the CFTR gene, exceeding 1,000, are responsible for the development of cystic
fibrosis. The most prevalent variant is F508del, observed in approximately 70% of affected individuals of
Caucasian descent in Canada, Northern Europe, and the United States<SupScrollLink label="14"/>. It is estimated that around 90% of
@@ -102,7 +116,7 @@ export function Description() {
<img src="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png"/>
</div>
<div className="col-4">
- <QuizQuestion name="schreibweise" front="What do the codes F508del and ΔF508 stand for?" back="they..."/>
+ <QuizQuestion name="schreibweise" front="What do the codes F508del and F508del stand for?" back="they..."/>
</div>
</div>
@@ -451,7 +465,7 @@ export function Description() {
<span property="schema:author" typeof="schema:Person">
<span property="schema:Name"> Lukacs, G.</span>
</span>
- <span property="schema:name"> CFTR: folding, misfolding and correcting the ΔF508 conformational defect. </span>
+ <span property="schema:name"> CFTR: folding, misfolding and correcting the F508del conformational defect. </span>
<i property="schema:publisher" typeof="schema:Organization"> Trends in molecular medicine</i>
<b property="issueNumber" typeof="PublicationIssue"> 18(2)</b>,
<span property="schema:pageBegin"> 81</span>-<span property="schema:pageEnd">91</span>
diff --git a/src/contents/example.tsx b/src/contents/example.tsx
index bb8780113fd98fa0191b3d97a297bcf31c00d20c..8397c77911c12cf98139bd8c6e9e1359d2006159 100644
--- a/src/contents/example.tsx
+++ b/src/contents/example.tsx
@@ -2,14 +2,14 @@
import { BlueInfoBox, BulbBox, InfoBox, NoteBox, QaBox, WarnBox } from "../components/Boxes";
import { BFHMoreButton, ButtonOne } from "../components/Buttons";
import Collapsible from "../components/Collapsible";
-import PieChart from "../components/Graph";
+import PieChart, { HowOftenTreatmentatients, MoreInfoOnTherapyBoth, OpenToGeneTherapyatients } from "../components/Graph";
import H1, { H2, H3, Hhighlight, Hhopp, Hsmoke, Hspoiler, Hwave } from "../components/Headings";
import { LoremMedium, LoremShort } from "../components/Loremipsum";
import SimpleSlider from "../components/Slider";
import React from 'react';
import { Bar, Doughnut, PolarArea } from 'react-chartjs-2';
import { Chart as ChartJS, Tooltip, Legend, BarElement, CategoryScale, LinearScale, Title, RadialLinearScale } from 'chart.js';
-import ProteinViewer from '../components/Fanzorviewer.tsx';
+/* import ProteinViewer from '../components/Fanzorviewer.tsx'; */
import { useTabNavigation } from "../utils/TabNavigation.tsx";
@@ -27,10 +27,12 @@ export function Example() {
useTabNavigation();
return (
<>
- <div className="container">
+
+
+{/* <div className="container">
<h1>Protein Structure Viewer</h1>
<ProteinViewer/>
- </div>
+ </div> */}
<h1> Here you can see what we can use</h1>
<h2>Collapisbles</h2>
@@ -44,6 +46,9 @@ export function Example() {
<div className="col">
<Collapsible title="Title" id="collapsible"> <LoremMedium></LoremMedium></Collapsible>
</div>
+ <HowOftenTreatmentatients/>
+ <OpenToGeneTherapyatients/>
+ <MoreInfoOnTherapyBoth/>
</div>
<h2>Boxes</h2>
<div className="row">
diff --git a/src/contents/igem-bielefeld.tsx b/src/contents/igem-bielefeld.tsx
index 27868d2e511c409ee2f51b5165c76f0ec1e8c882..abb8275ccbef9d003237e02c72b7c7483d564292 100644
--- a/src/contents/igem-bielefeld.tsx
+++ b/src/contents/igem-bielefeld.tsx
@@ -8,13 +8,17 @@ export function igemBielefeld() {
useTabNavigation();
return (
<>
+ <Section title="Bielefeld University" id="Bielefeld University">
+ ...
+ <img src="https://static.igem.wiki/teams/5247/photos/university/bielefeld-3381870.jpg"/>
+ </Section>
<Section title="History" id="History">
<div className="row">
<div className="col">
- <img src="https://static.igem.wiki/teams/5247/sponsors/uni-bielefeld-dunkel.png" style={{width:"50%", height:"50%"}}/>
+ <img src="https://static.igem.wiki/teams/5247/sponsors/uni-bielefeld-dunkel.png" style={{width:"40%", height:"60%"}}/>
</div>
<div className="col">
- <img src="https://static.igem.wiki/teams/5247/sponsors/cebitec-logo-hinterlegt.png" style={{width:"50%", height:"50%"}}/>
+ <img src="https://static.igem.wiki/teams/5247/sponsors/cebitec-logo-hinterlegt.png" style={{width:"20%", height:"50%", transform: "scale(1.5)"}}/>
</div>
</div>
<br/>
diff --git a/src/contents/methods.tsx b/src/contents/methods.tsx
index 31d0c8b96c52b689c44797fe478843329c067791..5a3906b947e6fca84598cca9d50756e684b4732a 100644
--- a/src/contents/methods.tsx
+++ b/src/contents/methods.tsx
@@ -1,17 +1,62 @@
+import { Section } from "../components/sections";
import { useTabNavigation } from "../utils/TabNavigation";
+import {H4} from "../components/Headings";
export function Methods() {
useTabNavigation();
return (
<>
- <div className="row">
- <div className="col">
-
+ <Section title="Introduction" id="Introduction">
+ ...
+ </Section>
+ <Section title="Patch Clamp" id="Patch Clamp">
+ <H4 text="Patch Clamp: A Key Tool in Electrophysiology"></H4>
+ <p>The patch clamp technique is a highly sensitive method for measuring ionic currents through individual ion channels in cells, making it a cornerstone of electrophysiological research. Initially developed by Erwin Neher and Bert Sakmann in the 1970s [1], this technique has evolved into various configurations, including the Whole-Cell and Single-Channel recordings [2], which provide critical insights into the functional properties of ion channels. </p>
+ <H4 text="Principles of the patch clamp technique"></H4>
+ <p>Patch clamp recording involves the use of a glass micropipette which is manufactured from a glass capillary through the use of a Micropipette Puller. The micropipette is then filled with an electrolyte solution, which is subsequently brought into contact with the cell membrane. By applying gentle suction, a high-resistance seal called giga seal is formed between the pipette tip and the membrane patch. This enables the measurement of ionic currents with minimal noise interference [3]. <strong>Whole-Cell Configuration</strong> records currents from the entire cell by rupturing the membrane patch, accessing the intracellular environment, and is useful for analysing overall ion channel activity and cellular responses. <strong>Single-Channel Recording</strong> measures currents through individual ion channels without rupturing the membrane, enabling high-resolution study of channel conductance, gating, and selectivity [2].</p>
+ <figure>
+ <iframe title="Bielefeld-CeBiTec: Patch Clamp Measurement (2024)" width="560" height="315" src="https://video.igem.org/videos/embed/0d948e57-5997-430a-a2df-815b71a2fc67?autoplay=1" frameBorder="0" allowFullScreen={true} sandbox="allow-same-origin allow-scripts allow-popups allow-forms"></iframe>
+ <figcaption> <b>Figure 1.</b> Microscopic recording of micropipette sealing of a HEK293 cell </figcaption>
+ </figure>
+
+
+ <p>The success of patch clamp experiments heavily depends on the composition of the solutions used. Typically, two main types of solutions are employed: The <strong>Pipette Solution</strong> in the micropipette mimics the intracellular environments, while the <strong>Bath Solution</strong> surrounds the cell and usually contains components that replicate the extracellular environment. Both solutions are meticulously designed to reflect the physiological conditions under which the cells operate, thereby ensuring that the measurements accurately reflect ion channel activity in a natural setting [2].</p>
+ <figure>
+ <img src="https://static.igem.wiki/teams/5247/photos/for-wiki-texts/meth-patch-clamp/bild-meth-patch-clamp.png" alt="Patch clamp setup"/>
+ <figcaption><b>Figure 2.</b> Patch clamp setup</figcaption>
+ </figure>
+ <H4 text="Application in CFTR gene prime editing validation"></H4>
+ <p>In our ongoing research project focusing on the treatment of cystic fibrosis (CF), our patch clamp measurements, performed in collaboration with Dr. Oliver Dräger from the Cellular Neurophysiology working group at Bielefeld University, serve as a powerful validation tool for the assessment of the functional correction of the CFTR gene, particularly the common F508del mutation, via prime editing. The patch clamp technique can be employed in this context to measure the resulting chloride ion channel activity which is altered by the mutation [4]. Whole-Cell recordings were performed to assess whether the corrected CFTR channels function similarly to those in healthy cells. If the chloride ion currents in the edited cells approach levels of healthy cells, this would strongly suggest successful gene editing and validate the functionality of our therapeutic approach.</p>
+
+
+
+ </Section>
+ <Section title="Cell Culture" id="Cell Lines">
+ <H4 text="HEK293 and HEK293T cell lines"></H4>
+ <p>For testing our prime editing approach, we needed an easy-to-handle cell line with a measurable high expression of CFTR and the CFTR F508del mutation. When talking to Mattijs Bulcaen from the Laboratory of Molecular Virology and Gene Therapy at KU Leuven, he recommended to use HEK293T cell lines overexpressing CFTR they had used. HEK293 cells are a very common immortalized human cell line derived from the kidneys of a female embryo. They are particularly suited to research due to their convenient handling and transfection properties. Basic HEK293 cells were provided to us by the Cellular and Molecular Biotechnology working group at Bielefeld University led by Prof. Dr. Kristian Müller, who is also one of the Principal Investigators of our team. HEK293T cells express an additional tsA1609 allele of the SV40 large T-antigen, allowing for replication of vectors containing the SV40 origin of replication.[2] Besides the native CFTR gene, which is not expressed in HEK cells, the HEK293T cell lines used in Leuven carry another copy of the gene embedded in an expression cassette. The cassette includes a CMV promoter, which is a standard promoter used for gene overexpression in human cells derived from the human Cytomegalovirus[4], as well as a puromycin resistance co-expressed with the CFTR allowing for continuous selection of CFTR expressing cells. The whole construct was stably inserted into the genome using lentiviral transduction.1,3 </p>
+ <figure>
+ <img src="https://static.igem.wiki/teams/5247/photos/for-wiki-texts/meth-used-cells/mikroskopie-hek293t.png" alt="Phase contrast image of HEK293T at 20x magnification"/>
+ <figcaption> <b>Figure 3.</b>Phase contrast image of HEK293T at 20x magnification</figcaption>
+ </figure>
+ <H4 text="CFBE41o- cell line "></H4>
+ <p>The CFBE41o- cell line, derived from bronchial epithelial cells of a one-year-old cystic fibrosis patient, serves as a vital model for studying cystic fibrosis. These cells closely mimic the physiological environment of the airway epithelium, allowing for more accurate studies on how CFTR mutations affect cell function and response to treatments. They were immortalized through calcium-phosphate-mediated transfection using a replication-defective pSVori plasmid that carries the simian virus 40 large T-antigen (SV40-LT). The plasmid's defective origin of replication prevents viral propagation, thus preserving essential physiological characteristics of the cells while enabling them to develop differentiated morphologies. CFBE41o- cells are homozygous for the F508del-CFTR mutation [1]. We are happy we got this cell line with permission from Prof. Dr. Zoya Ignatova, who is leader of a working group at the Institute for Biochemistry and Molecular Biology of Hamburg University and an iGEM supporter since a long time [6]. </p>
+ <H4 text="Human nasal epithelial cells (hNECs)"></H4>
+ <p>Human nasal epithelial cells were obtained by nasal brushing, a minimally invasive method. These cells function/act as primary cultures. Cultivated in air-liquid interface (ALI) cultures and apical-out airway organoids (AOAO), they serve as a suitable model to visualise the functional epithelium of the airways in a differentiated form. The in vivo aspects of an airway disease, such as CF, can be modelled using donors with those airway diseases (5) This model is therefore particularly suitable for testing our prime editing complex. </p>
+ <div className="row">
+ <div className="col">
+ <figure>
+
+ <figcaption> <b>Figure 4. </b> ALI cultures of hNECs: The active cilia beat frequency of differentiated human nasal epithelial cells (hNECs) in air-liquid interface (ALI) culture is visible. This ciliary movement is crucial for mucociliary transport, which contributes to the clearance of particles and pathogens in the respiratory tract. </figcaption>
+ </figure>
+ </div>
+ <div className="col">
+ <figure>
+
+ <figcaption> <b>Figure 5. </b> Apical-Out Airway Organoid (AOAO) culture: Visible apical-out airway organoids in action. These 3D structures, which mimic the airway epithelium, allow detailed study of cellular processes such as mucociliary transport and secretory activities, in which cilia and vesicles play a key role. </figcaption>
+ </figure>
+ </div>
</div>
- </div>
- <div className="row">
-
- </div>
+ </Section>
</>
);
}
diff --git a/src/contents/results.tsx b/src/contents/results.tsx
index 25bfd27b58d4caf464fcb3348f4e472176db0028..66701f8c2da8755c94229765e95d5340021acc89 100644
--- a/src/contents/results.tsx
+++ b/src/contents/results.tsx
@@ -3,6 +3,7 @@ import { H4 } from "../components/Headings";
import { LoremMedium } from "../components/Loremipsum";
import { Section, Subesction } from "../components/sections";
import { useTabNavigation } from "../utils/TabNavigation";
+import { H5 } from "../components/Headings";
export function Results() {
@@ -82,13 +83,47 @@ export function Results() {
<H4 text="Conclusion "/>
<LoremMedium/>
</Subesction>
- <Subesction title="LNP Synthesis " id="Experimental Design3">
- <H4 text="Goals"/>
+ <Subesction title="Delivery System" id="Experimental Design3">
+ <H4 text="Cayman LNP"/>
<p></p>
- <H4 text="Workflow"/>
+ <H5 text="Transfection"/>
+ <p></p>
+ <H5 text="FACS"/>
+ <p></p>
+ <H5 text="Zetapotential"/>
+ <p></p>
+ <H5 text="Dynamic Light Scattering (DLS)"/>
+ <p></p>
+ <H5 text="Scanning electron microscopy (SEM)"/>
+ <p></p>
+ <H5 text="cryo-TEM"/>
+ <p></p>
+ <H4 text="Corden LNP"/>
+ <H5 text="Transfection"/>
+ <p></p>
+ <H5 text="FACS"/>
+ <p></p>
+ <H5 text="Zetapotential"/>
+ <p></p>
+ <H5 text="Dynamic Light Scattering (DLS)"/>
+ <p></p>
+ <H5 text="Scanning electron microscopy (SEM)"/>
+ <p></p>
+ <H5 text="cryo-TEM"/>
+ <p></p>
+ <H4 text="AirBuddy"/>
+ <H5 text="Transfection"/>
+ <p></p>
+ <H5 text="FACS"/>
+ <p></p>
+ <H5 text="Zetapotential"/>
+ <p></p>
+ <H5 text="Dynamic Light Scattering (DLS)"/>
+ <p></p>
+ <H5 text="Scanning electron microscopy (SEM)"/>
+ <p></p>
+ <H5 text="cryo-TEM"/>
<p></p>
- <H4 text="Conclusion "/>
- <LoremMedium/>
</Subesction>
<Subesction title="Cellculture " id="Experimental Design4">
<H4 text="Goals"/>
diff --git a/src/contents/safety.tsx b/src/contents/safety.tsx
index 6391ef14df1220c3c194d2a6a966f8261f29aa8b..d7dae1737cb5073680db8d877765700cd7953ce7 100644
--- a/src/contents/safety.tsx
+++ b/src/contents/safety.tsx
@@ -98,7 +98,7 @@ export const Safety: React.FC = () =>{
<strong>HEK293T-3HA-F508del-CFTR cell line:</strong> The HEK293T-3HA-F508del-CFTR cell line is a modified HEK293T cell line that carries the F508del mutation in the CFTR gene, which is responsible for the most common mutation in cystic fibrosis. This mutation leads to a defective CFTR protein that impairs the normal function of the chloride channel. The cell line is therefore ideal for studying the effects of this mutation and for evaluating potential therapies for cystic fibrosis.
</p>
<p>
- <strong>CFBE41o- cell line:</strong> The CFBE41o- cell line, derived from the bronchial epithelial cells of a cystic fibrosis patient, is homozygous for the ΔF508-CFTR mutation and was essential for our cystic fibrosis research. A reduced CFTR expression level is present. The cell line carries the CFTR defect and can therefore represent a patient with CF. The cell line is used to test our mechanism. These cells were immortalized with a replication-defective plasmid that retains their physiological properties.
+ <strong>CFBE41o- cell line:</strong> The CFBE41o- cell line, derived from the bronchial epithelial cells of a cystic fibrosis patient, is homozygous for the F508del-CFTR mutation and was essential for our cystic fibrosis research. A reduced CFTR expression level is present. The cell line carries the CFTR defect and can therefore represent a patient with CF. The cell line is used to test our mechanism. These cells were immortalized with a replication-defective plasmid that retains their physiological properties.
When working with the HEK293T and CFBE41o- cell lines, it’s important to consider the minimal risks associated with their use. While not harmful on their own, the genetic modifications in HEK293T cells require careful handling to prevent accidental release or exposure. These cells, engineered to overexpress CFTR, including the F508del mutation, necessitate strict safety measures like regular monitoring and proper waste disposal to comply with S1 laboratory standards. Similarly, CFBE41o- cells, due to their genetic modifications and disease relevance, require careful handling to avoid cross-contamination and ensure biosafety.
</p>
<p>
@@ -129,9 +129,13 @@ export const Safety: React.FC = () =>{
<p>
In our S2 laboratory, the harvested nasal epithelial cells that serve as primary cultures undergo a comprehensive HHH test (link zu primär Kulturen) to ensure their safety and suitability for further experiments. This test is crucial to ensure that we can subsequently work safely with these cells in the S1 range without the risk of contamination or unwanted release of biological material.
</p>
- <div className="col">
- <img src="https://static.igem.wiki/teams/5247/photos/biosafety/s2/s2-lab.jpeg" width="50%" height="50%"/>
- </div>
+
+ <div className="figure-wrapper">
+ <figure>
+ <img src="https://static.igem.wiki/teams/5247/photos/biosafety/s2/s2-lab.jpeg" style={{height: "10%"}}/>
+ <figcaption> <b>Figure x.</b> </figcaption>
+ </figure>
+ </div>
</Section>
<Section title="Biosafety" id="Biosafety">
<Subesction title="Safety aspects of our PrimeGuide" id="Biosafety1">
@@ -140,32 +144,32 @@ export const Safety: React.FC = () =>{
</p>
<H4 text="PAM disrupt" ></H4>
<p>
- A key safety mechanism incorporated in our design of the Prime Editing complex is the disruption of the PAM sequence. For the nickase enzyme to function properly, it must bind directly to the DNA strand, a process that is facilitated by the presence of a specific sequence called the PAM (Protospacer Adjacent Motif). This critical interaction occurs through the recognition of the PAM sequence by the nickase itself. To achieve PAM disruption, the pegRNA (prime editing guide RNA) is specifically designed in a way so that the PAM sequence is situated within the reverse transcription template (RTT) of the pegRNA. By introducing a silent mutation within the RT template into the PAM sequence. Therefore the PAM sequence is effectively eliminated after the gene editing process is successfully completed [1]. As a result of that, the PAM sequence is no longer present on the DNA strand, preventing the nickase from binding again at the same location. This reduction in repeated or undesired binding of the nickase enhances the safety of our prime editing complex, minimizing the risk of unintended edits or off-target effects in subsequent steps. Ultimately, this feature contributes very much to the overall safety and reliability of the prime editing process.
+ A key safety mechanism incorporated in our design of the Prime Editing complex is the disruption of the PAM sequence. For the nickase enzyme to function properly, it must bind directly to the DNA strand, a process that is facilitated by the presence of a specific sequence called the PAM (Protospacer Adjacent Motif). This critical interaction occurs through the recognition of the PAM sequence by the nickase itself. To achieve PAM disruption, the pegRNA (prime editing guide RNA) is specifically designed in a way so that the PAM sequence is situated within the reverse transcription template (RTT) of the pegRNA. By introducing a silent mutation within the RT template into the PAM sequence. Therefore the PAM sequence is effectively eliminated after the gene editing process is successfully completed <SupScrollLink label="1"/>. As a result of that, the PAM sequence is no longer present on the DNA strand, preventing the nickase from binding again at the same location. This reduction in repeated or undesired binding of the nickase enhances the safety of our prime editing complex, minimizing the risk of unintended edits or off-target effects in subsequent steps. Ultimately, this feature contributes very much to the overall safety and reliability of the prime editing process.
</p>
<H4 text="pegRNA design - Spacer"></H4>
<p>
- Biosafety is also guaranteed by the careful selection of the spacer, which plays a critical role in guiding the complex to its intended target site [2]. To ensure both precision and safety, we meticulously chose and rigorously checked the spacer using the CRISPick software [3]. This allowed us to evaluate whether our Spacer would be likely to target other regions than our target site and therefore allowing us to analyse and predict potential off-target effects, ensuring that erroneous edits are minimised. By optimising the spacer selection, we have not only significantly enhanced the overall editing efficiency, striking a balance between precision and performance, but especially ensured the utmost accuracy in directing the Prime Editor, further contributing to the safety of the editing process. [Bild 1]
+ Biosafety is also guaranteed by the careful selection of the spacer, which plays a critical role in guiding the complex to its intended target site <SupScrollLink label="2"/>. To ensure both precision and safety, we meticulously chose and rigorously checked the spacer using the CRISPick software <SupScrollLink label="3"/>. This allowed us to evaluate whether our Spacer would be likely to target other regions than our target site and therefore allowing us to analyse and predict potential off-target effects, ensuring that erroneous edits are minimised. By optimising the spacer selection, we have not only significantly enhanced the overall editing efficiency, striking a balance between precision and performance, but especially ensured the utmost accuracy in directing the Prime Editor, further contributing to the safety of the editing process. [Bild 1]
</p>
<H4 text="Riboswitch"></H4>
<p>
- Riboswitches are segments of an RNA strand that bind to small molecules, causing them to change their secondary structure by forming hairpin structures. This process regulates gene expression at the translation level by preventing ribosomes from binding at the RBS and translating the coding region on the RNA strand. 0For our project we also considered an ion-sensitive riboswitch, specifically dependent on sodium ions (Naâº), as a regulatory mechanism. The secondary structure of this riboswitch prevents the binding of ribosomes to the ribosome binding site (RBS) under normal conditions, thus inhibiting the translation of the subsequent mRNA. When sodium ions bind to the riboswitch, a structural change occurs, exposing the RBS, which allows for the translation of the mRNA and the production of our fusion protein which is the main component of our prime editing system and therefore of enormous importance for it to work [4]. In the context of the CFTR mutation and its effects on the cell, the elevated Na⺠levels play a crucial role. Due to the dysfunctional CFTR channel, which fails to properly function as a chloride channel, the ENaC channel (epithelial sodium channel) becomes upregulated. This upregulation results in an increased transport of sodium ions into the cell, leading to a higher intracellular sodium concentration. This elevated Na⺠concentration creates a specific ionic environment that could potentially be utilized to regulate our Prime-Editing complex in a targeted manner. Given these specific ionic changes in the cell, we could have a disease-specific regulation of our Prime-Editing system based on the ionic situation typical of this condition. However, despite the initial promise of this approach, after further research, we concluded that the riboswitch, even considering the ion levels within epithelial cells, is overall too nonspecific and therefore too unreliable as a regulatory mechanism. Although the ion levels in CFTR cells are much lower, there are still low concentrations of sodium ions, which can lead to the riboswitch not being completely switched off.
+ Riboswitches are segments of an RNA strand that bind to small molecules, causing them to change their secondary structure by forming hairpin structures. This process regulates gene expression at the translation level by preventing ribosomes from binding at the RBS and translating the coding region on the RNA strand. 0For our project we also considered an ion-sensitive riboswitch, specifically dependent on sodium ions (Naâº), as a regulatory mechanism. The secondary structure of this riboswitch prevents the binding of ribosomes to the ribosome binding site (RBS) under normal conditions, thus inhibiting the translation of the subsequent mRNA. When sodium ions bind to the riboswitch, a structural change occurs, exposing the RBS, which allows for the translation of the mRNA and the production of our fusion protein which is the main component of our prime editing system and therefore of enormous importance for it to work <SupScrollLink label="4"/>. In the context of the CFTR mutation and its effects on the cell, the elevated Na⺠levels play a crucial role. Due to the dysfunctional CFTR channel, which fails to properly function as a chloride channel, the ENaC channel (epithelial sodium channel) becomes upregulated. This upregulation results in an increased transport of sodium ions into the cell, leading to a higher intracellular sodium concentration. This elevated Na⺠concentration creates a specific ionic environment that could potentially be utilized to regulate our Prime-Editing complex in a targeted manner. Given these specific ionic changes in the cell, we could have a disease-specific regulation of our Prime-Editing system based on the ionic situation typical of this condition. However, despite the initial promise of this approach, after further research, we concluded that the riboswitch, even considering the ion levels within epithelial cells, is overall too nonspecific and therefore too unreliable as a regulatory mechanism. Although the ion levels in CFTR cells are much lower, there are still low concentrations of sodium ions, which can lead to the riboswitch not being completely switched off.
[Bild 2]
As a further approach to developing alternative riboswitch variants, we considered the possibility of an RNA-regulated riboswitch targeting the defective mRNA sequence of the genetically defective CFTR gene. The basic idea behind this concept was that the riboswitch specifically binds to a region on the CFTR mRNA containing the F508Δ mutation. This binding should induce a structural change in the riboswitch on our prime editing complex’s mRNA that ultimately leads to exposure of the RBS to allow translation of the downstream sequence. This mechanism would be designed to react specifically to the defective CFTR mRNA and only cause a change in the secondary structure in the presence of the specific mutation. The riboswitch could thus ensure selective and disease-specific activation of our prime editing complex, which would be of particular interest in the context of genetic diseases such as cystic fibrosis. However, we did not pursue this approach any further. A major reason for this was the lack of sufficient literature providing a sound scientific basis for this specific application of a riboswitch. In
addition, our research steered us in a different direction, particularly with regard to the alternative mechanism involving the XBP1 intron to regulate the prime editing system. This alternative seemed more promising and was based on an established regulatory mechanism that is triggered by cellular stress and specifically responds to misfolding processes.
</p>
<H4 text="XBP1 Intron"></H4>
<p>
- After extensive research, we discovered a regulatory system in eukaryotic cells, the XBP1 mechanism. The activation of XBP1 is an important mechanism that occurs as part of the Unfolded Protein Response (UPR), a cellular stress response triggered by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The ER is a key cellular component responsible for protein folding and transport. When many misfolded proteins accumulate in the ER, a specific regulatory mechanism is activated to reduce the stress on the ER. XBP1 activation is controlled by a protein called IRE1α, which is embedded in the ER membrane. IRE1α acts as a sensor for protein misfolding stress in the ER. Once IRE1α detects misfolded proteins, it dimerizes and becomes activated through autophosphorylation. This activation switches on the endoribonuclease activity of IRE1α, which is a crucial step in the activation of XBP1. The mRNA for XBP1 is continuously transcribed in the nucleus and transported to the cytoplasm, where it contains an intron that is not normally spliced out. This intron contains a stop codon, preventing the translation of a functional XBP1 protein. However, when ER stress activates IRE1α, the endoribonuclease domain of IRE1α splices this intron out of the XBP1 mRNA. This is an unconventional splicing event, as it occurs in the cytoplasm rather than in the nucleus. Once the intron is removed, the spliced XBP1 mRNA can be translated into a functional XBP1 protein. This activated XBP1 acts as a transcription factor, turning on genes that increase the protein-folding capacity of the ER and promote the degradation of misfolded proteins. In this way, XBP1 helps the cell cope with ER stress and restore balance in the protein-folding process. Thus, this mechanism originally functions within the cell in the context of ER stress to maintain ER function when protein folding is disrupted. [5] [6] Our idea was therefore to integrate this intron into the mRNA encoding our prime-editing complex and thus use this mechanism to ensure that a functional prime editor is only synthesized when there is a high accumulation of misfolded proteins in the cell (similar to F508del). This would therefore represent an optimal safety aspect, as our fusion protein, which is essential for prime editing, cannot be fully synthesised as long as the genetic defect is not present in the cell. Accordingly, this provides the security that no healthy cells, as well as correctly edited cells, cannot be edited, which is an enormous contribution to biosafety. However, there was too much uncertainty about the extent to which other factors, such as misfolded proteins that are not associated with the CFTR protein, play a role in this mechanism. And since we could not and did not want to take the risk of such factors initiating the system, we decided against using it. To clarify this unknown correlation, we have considered a future experiment in which we want to switch this intron in front of a fluorescent marker and express it in cells with defective CFTR in order to confirm/investigate the dependence of intron splicing and the presence of CFTR F508del.
+ After extensive research, we discovered a regulatory system in eukaryotic cells, the XBP1 mechanism. The activation of XBP1 is an important mechanism that occurs as part of the Unfolded Protein Response (UPR), a cellular stress response triggered by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The ER is a key cellular component responsible for protein folding and transport. When many misfolded proteins accumulate in the ER, a specific regulatory mechanism is activated to reduce the stress on the ER. XBP1 activation is controlled by a protein called IRE1α, which is embedded in the ER membrane. IRE1α acts as a sensor for protein misfolding stress in the ER. Once IRE1α detects misfolded proteins, it dimerizes and becomes activated through autophosphorylation. This activation switches on the endoribonuclease activity of IRE1α, which is a crucial step in the activation of XBP1. The mRNA for XBP1 is continuously transcribed in the nucleus and transported to the cytoplasm, where it contains an intron that is not normally spliced out. This intron contains a stop codon, preventing the translation of a functional XBP1 protein. However, when ER stress activates IRE1α, the endoribonuclease domain of IRE1α splices this intron out of the XBP1 mRNA. This is an unconventional splicing event, as it occurs in the cytoplasm rather than in the nucleus. Once the intron is removed, the spliced XBP1 mRNA can be translated into a functional XBP1 protein. This activated XBP1 acts as a transcription factor, turning on genes that increase the protein-folding capacity of the ER and promote the degradation of misfolded proteins. In this way, XBP1 helps the cell cope with ER stress and restore balance in the protein-folding process. Thus, this mechanism originally functions within the cell in the context of ER stress to maintain ER function when protein folding is disrupted. <SupScrollLink label="5"/><SupScrollLink label="6"/> Our idea was therefore to integrate this intron into the mRNA encoding our prime-editing complex and thus use this mechanism to ensure that a functional prime editor is only synthesized when there is a high accumulation of misfolded proteins in the cell (similar to F508del). This would therefore represent an optimal safety aspect, as our fusion protein, which is essential for prime editing, cannot be fully synthesised as long as the genetic defect is not present in the cell. Accordingly, this provides the security that no healthy cells, as well as correctly edited cells, cannot be edited, which is an enormous contribution to biosafety. However, there was too much uncertainty about the extent to which other factors, such as misfolded proteins that are not associated with the CFTR protein, play a role in this mechanism. And since we could not and did not want to take the risk of such factors initiating the system, we decided against using it. To clarify this unknown correlation, we have considered a future experiment in which we want to switch this intron in front of a fluorescent marker and express it in cells with defective CFTR in order to confirm/investigate the dependence of intron splicing and the presence of CFTR F508del.
</p>
</Subesction>
<Subesction title="Safety aspects of our Airbuddy" id="Biosafety2">
<H4 text="SORT LNP and Cytotoxicity"></H4>
<p>
- We have carefully considered the biosafety aspects of our delivery system, starting with the decision between Adeno-associated viruses (AAV) or LNPs as delivery systems. Our comparison revealed that the biocompatibility and safety of LNPs are paramount for our approach. That is why we chose selective organ-targeting (SORT) lipid nanoparticles (LNPs) [7] in the context of targeted pulmonary mRNA delivery. One of our primary concerns with the LNP was the potential cytotoxicity of polyethylene glycol (PEG), a common stabilizing agent in LNP formulations. Aware of the immune responses PEG can trigger, potentially leading to cytotoxicity [8], we aimed at optimizing its concentration in our SORT LNPs to minimize such reactions while maintaining therapeutic efficacy. By the use of low molecular weight PEG, we addressed this problem. To test weather our approach succeeded, we conducted MTT and proliferation assays to ensure that our LNP posed no cytotoxicity risks.
+ We have carefully considered the biosafety aspects of our delivery system, starting with the decision between Adeno-associated viruses (AAV) or LNPs as delivery systems. Our comparison revealed that the biocompatibility and safety of LNPs are paramount for our approach. That is why we chose selective organ-targeting (SORT) lipid nanoparticles (LNPs) <SupScrollLink label="7"/> in the context of targeted pulmonary mRNA delivery. One of our primary concerns with the LNP was the potential cytotoxicity of polyethylene glycol (PEG), a common stabilizing agent in LNP formulations. Aware of the immune responses PEG can trigger, potentially leading to cytotoxicity <SupScrollLink label="8"/>, we aimed at optimizing its concentration in our SORT LNPs to minimize such reactions while maintaining therapeutic efficacy. By the use of low molecular weight PEG, we addressed this problem. To test weather our approach succeeded, we conducted MTT and proliferation assays to ensure that our LNP posed no cytotoxicity risks.
</p>
<H4 text="Precision of our SORT LNP"></H4>
<p>
- To further improve safety, we focused on reducing off-target effects. By incorporating specific SORT molecules, such as permanently cationic lipids like DOTAP, we ensured that the nanoparticles are systematically directed to the lungs. This precise targeting is particularly beneficial for respiratory diseases, as it enhances therapeutic effectiveness while limiting the impact on non-target organs. Our outlook of antibody conjugation as surface modification of our LNP for cell type-specific delivery, more exactly club cells [9] and ionocytes [10] as CFTR-expressing lung epithelial cells, would round off this aspect.
+ To further improve safety, we focused on reducing off-target effects. By incorporating specific SORT molecules, such as permanently cationic lipids like DOTAP, we ensured that the nanoparticles are systematically directed to the lungs. This precise targeting is particularly beneficial for respiratory diseases, as it enhances therapeutic effectiveness while limiting the impact on non-target organs. Our outlook of antibody conjugation as surface modification of our LNP for cell type-specific delivery, more exactly club cells <SupScrollLink label="9"/> and ionocytes <SupScrollLink label="10"/> as CFTR-expressing lung epithelial cells, would round off this aspect.
</p>
<p>
In summary, our design strategy emphasizes both safety and efficacy. The careful optimization of components like PEG 2000 and the use of targeted delivery molecules allow SORT LNPs to deliver therapeutic agents directly to the lungs, reducing systemic exposure and minimizing side effects. This targeted approach ensures more effective treatments, especially for conditions requiring localized intervention.
@@ -192,19 +196,19 @@ export const Safety: React.FC = () =>{
Given the sensitive nature of genome editing, our project presents specific biosecurity concerns that need to be assessed and mitigated.
</p>
<p>
- <strong>Dual-Use Potential:</strong> One of the main biosecurity risks is the potential for dual-use of the Prime Editing technology. The system we are developing, while intended for therapeutic use, could be misused to target other genes or genomes for malicious purposes.[11] This includes the possibility of weaponizing the technology to induce harmful genetic changes in crops, animals, or even humans. The modular design of our plasmid system, although intended to facilitate optimization, could be exploited to exchange components for harmful applications, thereby increasing the risk of misuse.
+ <strong>Dual-Use Potential:</strong> One of the main biosecurity risks is the potential for dual-use of the Prime Editing technology. The system we are developing, while intended for therapeutic use, could be misused to target other genes or genomes for malicious purposes. <SupScrollLink label="11"/> This includes the possibility of weaponizing the technology to induce harmful genetic changes in crops, animals, or even humans. The modular design of our plasmid system, although intended to facilitate optimization, could be exploited to exchange components for harmful applications, thereby increasing the risk of misuse.
</p>
<p>
- <strong>Unintendend Dissemination:</strong> Since our approach uses mRNA delivered via LNPs, there is a risk of unintended dissemination into the environment. If the LNPs are not adequately contained or disposed of, there is a possibility that they could be absorbed by non-target organisms, potentially leading to off-target genetic modifications.[12] In addition, the mRNA itself could theoretically be transferred between cells, especially if taken up by unintended hosts, raising concerns about unintentional spread in the environment.
+ <strong>Unintendend Dissemination:</strong> Since our approach uses mRNA delivered via LNPs, there is a risk of unintended dissemination into the environment. If the LNPs are not adequately contained or disposed of, there is a possibility that they could be absorbed by non-target organisms, potentially leading to off-target genetic modifications.<SupScrollLink label="12"/> In addition, the mRNA itself could theoretically be transferred between cells, especially if taken up by unintended hosts, raising concerns about unintentional spread in the environment.
</p>
<p>
- <strong>Unauthorized Access:</strong> The genetic constructs and the detailed methodology of our Prime Editing system must be securely stored and protected.[13] If unauthorized individuals were to gain access to the plasmids, LNP formulations, or editing protocols, there is a risk of the technology being replicated or adapted for unintended, potentially harmful uses. This highlights the importance of proper biosecurity protocols in both physical and digital storage of our project materials.
+ <strong>Unauthorized Access:</strong> The genetic constructs and the detailed methodology of our Prime Editing system must be securely stored and protected.<SupScrollLink label="13"/> If unauthorized individuals were to gain access to the plasmids, LNP formulations, or editing protocols, there is a risk of the technology being replicated or adapted for unintended, potentially harmful uses. This highlights the importance of proper biosecurity protocols in both physical and digital storage of our project materials.
</p>
<p>
- <strong>Synthetic Biology and information Sharing:</strong> The ease of synthesizing genetic material means that our project information could potentially be used to order similar constructs from commercial synthesis providers.[14] While these providers follow biosecurity guidelines, the increasing accessibility of synthetic biology raises the concern of our Prime Editing system being reproduced or modified without our knowledge. This includes potential attempts to bypass safety mechanisms or create variants that evade current regulatory frameworks.
+ <strong>Synthetic Biology and information Sharing:</strong> The ease of synthesizing genetic material means that our project information could potentially be used to order similar constructs from commercial synthesis providers.<SupScrollLink label="14"/> While these providers follow biosecurity guidelines, the increasing accessibility of synthetic biology raises the concern of our Prime Editing system being reproduced or modified without our knowledge. This includes potential attempts to bypass safety mechanisms or create variants that evade current regulatory frameworks.
</p>
<p>
- <strong>Public Perception and Miscommunication:</strong> There is a biosecurity risk in how our project's technology is communicated to the public.[15] Miscommunication or misunderstanding of the project’s intent and capabilities could lead to misinformation, fear, or even attempts to replicate the technology outside of controlled and regulated environments. This could undermine public trust in legitimate therapeutic uses of genome-editing technologies and potentially facilitate misuse.
+ <strong>Public Perception and Miscommunication:</strong> There is a biosecurity risk in how our project's technology is communicated to the public.<SupScrollLink label="15"/> Miscommunication or misunderstanding of the project’s intent and capabilities could lead to misinformation, fear, or even attempts to replicate the technology outside of controlled and regulated environments. This could undermine public trust in legitimate therapeutic uses of genome-editing technologies and potentially facilitate misuse.
</p>
</Subesction>
<Subesction title="Managing Risks" id="Biosecurity3">
@@ -277,13 +281,13 @@ export const Safety: React.FC = () =>{
<Section title="Bioethics" id="Bioethics">
<div>
<p>
- Bioethics is an interdisciplinary field of research that addresses ethical issues pertaining to the life sciences and medical research. It plays a pivotal role in contemporary research, particularly in projects that employ human samples or data. This is due to the fact that in these cases, the protection of the rights and dignity of the people involved is of the utmost importance <SupScrollLink label="1"/> [16]. In order to ascertain the necessity for an ethics application, an interview was conducted with Eva-Maria Berens, the scientific director of the office of the Ethics Committee at Bielefeld University, as part of the current research project. Following a comprehensive review, it was concluded that an ethics application was not necessary for the specific research project. Nevertheless, a comprehensive patient consent form was developed in conjunction with Eva-Maria Berens to guarantee that the donors of their samples are adequately informed and provide their consent of their own volition. The document guarantees that all pertinent information regarding sample collection, utilisation and storage is provided in an intelligible format. Furthermore, an interview was conducted with Dr. Timm Weber, a representative of the biobank, to discuss the topic of bioethics in greater depth. During the course of the interviews, the ethical aspects of sample storage and utilisation within the biobank were discussed in detail. Particular attention was paid to the responsible handling and protection of the rights of the test subjects. The discussion of bioethics in both interviews emphasises the relevance of ethical principles for research and ensures that it is conducted in accordance with the highest ethical standards.
+ Bioethics is an interdisciplinary field of research that addresses ethical issues pertaining to the life sciences and medical research. It plays a pivotal role in contemporary research, particularly in projects that employ human samples or data. This is due to the fact that in these cases, the protection of the rights and dignity of the people involved is of the utmost importance <SupScrollLink label="16"/>. In order to ascertain the necessity for an ethics application, an interview was conducted with Eva-Maria Berens, the scientific director of the office of the Ethics Committee at Bielefeld University, as part of the current research project. Following a comprehensive review, it was concluded that an ethics application was not necessary for the specific research project. Nevertheless, a comprehensive patient consent form was developed in conjunction with Eva-Maria Berens to guarantee that the donors of their samples are adequately informed and provide their consent of their own volition. The document guarantees that all pertinent information regarding sample collection, utilisation and storage is provided in an intelligible format. Furthermore, an interview was conducted with Dr. Timm Weber, a representative of the biobank, to discuss the topic of bioethics in greater depth. During the course of the interviews, the ethical aspects of sample storage and utilisation within the biobank were discussed in detail. Particular attention was paid to the responsible handling and protection of the rights of the test subjects. The discussion of bioethics in both interviews emphasises the relevance of ethical principles for research and ensures that it is conducted in accordance with the highest ethical standards.
</p>
</div>
<Subesction title="Gene Therapy" id="Bioethics1">
<div>
<p>
- The potential of gene therapy to treat genetic diseases is promising, but it is also associated with significant ethical issues. One of the principal challenges is ensuring the safety of the procedure and the potential for unforeseen long-term consequences. Such consequences may only become apparent years after the genetic intervention has taken place. The modification of the germline, which affects not only the individual but also future generations, is a particularly sensitive issue. This gives rise to the question of the extent to which the decisions made today will influence future generations without their consent, thereby jeopardising intergenerational justice <SupScrollLink label="2"/> [17]. Another ethical issue is the potential for misuse for eugenic purposes. While the current focus is on combating disease, future applications could be aimed at 'optimising' human traits, which could result in a worsening of social inequalities. Access to gene therapy is also a significant issue. High costs could limit access to wealthy population groups, which would reinforce existing inequalities <SupScrollLink label="3"/> [18]. The issue of informed consent is also a key aspect. Many patients do not have the necessary knowledge to fully understand the complex risks, which raises ethical questions about their decision-making capacity. Overall, the debate around gene therapy highlights that ethical considerations such as safety, justice and patient rights need to be considered alongside scientific progress <SupScrollLink label="4"/> [19].
+ The potential of gene therapy to treat genetic diseases is promising, but it is also associated with significant ethical issues. One of the principal challenges is ensuring the safety of the procedure and the potential for unforeseen long-term consequences. Such consequences may only become apparent years after the genetic intervention has taken place. The modification of the germline, which affects not only the individual but also future generations, is a particularly sensitive issue. This gives rise to the question of the extent to which the decisions made today will influence future generations without their consent, thereby jeopardising intergenerational justice <SupScrollLink label="17"/>. Another ethical issue is the potential for misuse for eugenic purposes. While the current focus is on combating disease, future applications could be aimed at 'optimising' human traits, which could result in a worsening of social inequalities. Access to gene therapy is also a significant issue. High costs could limit access to wealthy population groups, which would reinforce existing inequalities <SupScrollLink label="18"/>. The issue of informed consent is also a key aspect. Many patients do not have the necessary knowledge to fully understand the complex risks, which raises ethical questions about their decision-making capacity. Overall, the debate around gene therapy highlights that ethical considerations such as safety, justice and patient rights need to be considered alongside scientific progress <SupScrollLink label="19"/>.
</p>
</div>
</Subesction>
@@ -291,11 +295,11 @@ export const Safety: React.FC = () =>{
<div>
<H4 text="Introduction of primary cultures"></H4>
<p>
- A primary culture is defined as a cell culture that is isolated directly from the tissue of an organism. In our case, the organism is human. The cells are then cultivated in a controlled environment, namely an S2 laboratory <SupScrollLink label="5"/> [20]. Primary cultures are a fundamental biomedical research tool, widely regarded as indispensable due to their capacity for realistic modelling of complex cell interactions. Primary cells are derived directly from the tissue of an organism and, as a consequence, they essentially retain their original properties. Consequently, they mirror the authentic conditions of the target tissue, which is vital for accurately assessing the impact of a therapeutic agent. In contrast, HEK cells represent transformed cell lines that exhibit physiological properties distinct from those of target cells in the human body. The effect of a therapeutic agent is typically limited to a specific cell type. The investigation of cell-specific effects and reactions of an active substance is feasible with the use of primary cells, as these possess the functional characteristics inherent to the cell type under consideration. Although HEK cells are relatively straightforward to cultivate, they are less representative of a number of tissue types and may activate other signalling pathways. The authenticity of the receptors and signalling pathways is guaranteed, as primary cells show the natural expression of receptors, ion channels and other cellular mechanisms. HEK cells are often genetically modified to express specific receptors, which can be useful for simple test systems. However, this does not reflect the complex environment of a real tissue. Given the sensitivity of primary cultures to environmental influences, thus resulting in higher risk of a contamination, it is imperative that researchers employ special safety measures to ensure the safety of themselves and the integrity of the cells. Primary cultures are employed extensively in the development of vaccines, cancer research and the investigation of basic cell processes.
+ A primary culture is defined as a cell culture that is isolated directly from the tissue of an organism. In our case, the organism is human. The cells are then cultivated in a controlled environment, namely an S2 laboratory <SupScrollLink label="20"/>. Primary cultures are a fundamental biomedical research tool, widely regarded as indispensable due to their capacity for realistic modelling of complex cell interactions. Primary cells are derived directly from the tissue of an organism and, as a consequence, they essentially retain their original properties. Consequently, they mirror the authentic conditions of the target tissue, which is vital for accurately assessing the impact of a therapeutic agent. In contrast, HEK cells represent transformed cell lines that exhibit physiological properties distinct from those of target cells in the human body. The effect of a therapeutic agent is typically limited to a specific cell type. The investigation of cell-specific effects and reactions of an active substance is feasible with the use of primary cells, as these possess the functional characteristics inherent to the cell type under consideration. Although HEK cells are relatively straightforward to cultivate, they are less representative of a number of tissue types and may activate other signalling pathways. The authenticity of the receptors and signalling pathways is guaranteed, as primary cells show the natural expression of receptors, ion channels and other cellular mechanisms. HEK cells are often genetically modified to express specific receptors, which can be useful for simple test systems. However, this does not reflect the complex environment of a real tissue. Given the sensitivity of primary cultures to environmental influences, thus resulting in higher risk of a contamination, it is imperative that researchers employ special safety measures to ensure the safety of themselves and the integrity of the cells. Primary cultures are employed extensively in the development of vaccines, cancer research and the investigation of basic cell processes.
</p>
<H4 text="Ethics in work with primary cultures"></H4>
<p>
- The term 'ethics' is used to describe the examination of moral principles that determine the behaviour of individuals or groups <SupScrollLink label="6"/> [21]. In a scientific context, the term 'ethics' encompasses the examination of the moral justifiability of actions and decisions, particularly with regard to the welfare of living beings and the responsible use of resources <SupScrollLink label="7"/> [22]. The isolation of primary cells from living organisms raises ethical questions, particularly in the case of human or animal tissue. In the context of research with animal primary cells, careful consideration must be given to the need for animal suffering and the potential benefits of the research <SupScrollLink label="8"/> [23]. An ethical dilemma frequently arises from the fact that primary cells offer the most meaningful data from a biological standpoint, yet their production is associated with challenges. In this context, the necessity of primary cell cultures is called into question, and the promotion of alternative methods, such as artificially produced tissues or organoids, is advocated where feasible. It is of crucial importance to emphasize the necessity of ethical responsibility in the collection of primary cultures. It is of the utmost importance that the procedure is carried out with consideration for the rights, and particularly the well-being of the donor. The removal of cells or tissue must be medically justifiable and, moreover, ethically justifiable in every case. To this end, the potential for research use and the possible risks and burdens for the donor must be weighed against each other to ensure careful consideration. However, it is also particularly important to ensure that the donor is involved in the entire process and is able to make an informed decision. The purpose of the research, the use of the cells and possible consequences must also be made transparent at all times.
+ The term 'ethics' is used to describe the examination of moral principles that determine the behaviour of individuals or groups <SupScrollLink label="21"/>. In a scientific context, the term 'ethics' encompasses the examination of the moral justifiability of actions and decisions, particularly with regard to the welfare of living beings and the responsible use of resources <SupScrollLink label="22"/>. The isolation of primary cells from living organisms raises ethical questions, particularly in the case of human or animal tissue. In the context of research with animal primary cells, careful consideration must be given to the need for animal suffering and the potential benefits of the research <SupScrollLink label="23"/>. An ethical dilemma frequently arises from the fact that primary cells offer the most meaningful data from a biological standpoint, yet their production is associated with challenges. In this context, the necessity of primary cell cultures is called into question, and the promotion of alternative methods, such as artificially produced tissues or organoids, is advocated where feasible. It is of crucial importance to emphasize the necessity of ethical responsibility in the collection of primary cultures. It is of the utmost importance that the procedure is carried out with consideration for the rights, and particularly the well-being of the donor. The removal of cells or tissue must be medically justifiable and, moreover, ethically justifiable in every case. To this end, the potential for research use and the possible risks and burdens for the donor must be weighed against each other to ensure careful consideration. However, it is also particularly important to ensure that the donor is involved in the entire process and is able to make an informed decision. The purpose of the research, the use of the cells and possible consequences must also be made transparent at all times.
The obtaining of informed consent represents a fundamental aspect of ethical practice in the collection of primary cells. This process must encompass not only a formal consent procedure, but also the provision of comprehensive information to donors regarding the collection, utilisation and prospective future applications of the cells. The act of consent must be given freely and without undue influence, and donors must be fully aware of the consequences of their participation. Furthermore, donors must be granted the right to revoke their consent at any time without consequence. Prior to the collection of cells, a comprehensive discussion is held with the donor, during which all pertinent details are elucidated and any queries or concerns they may have, are addressed. This guarantees that the donor is adequately informed and is thus able to make an autonomous decision based on a comprehensive understanding of the procedure.
The protection of privacy and confidentiality is of paramount importance when working with primary cultures. Given that primary cultures are predominantly human tissue, they contain genetic information and other personal data that is sensitive and deserving of protection. It is therefore of great importance that the data is anonymized and kept strictly confidential in order to protect the identity of the donor.
Every person who has access to the data or samples must be obliged to comply with confidentiality standards. It must be ensured that all legal requirements for data protection are met, including compliance with data protection laws such as the GDPR in the EU.
diff --git a/src/contents/team.tsx b/src/contents/team.tsx
index 865f45ecb6e35060db175d8ee8df4de00467fdfe..87ed6412ea4b8cf803633a836ecb3a9d6b617459 100644
--- a/src/contents/team.tsx
+++ b/src/contents/team.tsx
@@ -47,7 +47,10 @@ function createSteckbriefe(data: Array<SteckbriefInterface>){
// Jobs
var jobs = "";
for (let i = 0; i < data[index].igemjob.length; i++) {
- if (i + 1 == data[index].igemjob.length ) {
+ if (data[index].igemjob.length == 1) {
+ jobs += data[index].igemjob[i]
+ }
+ else if (i + 1 == data[index].igemjob.length ) {
jobs += " and " + data[index].igemjob[i];
}
else if(i + 2 == data[index].igemjob.length){
@@ -128,7 +131,7 @@ function createSteckbriefe(data: Array<SteckbriefInterface>){
<div className="col-4 brieffacts">
<br/><br/> {funfactlist} {facts}
</div>
- </div> <div className="row" style={{marginTop: "1rem", marginBottom: "1rem"}}> <div className="col-2"> {frontbutton} {backbutton}</div> <div className="col"><details className={frontbriefclass} ><summary> <b>Personal motivation and challenges</b> </summary><div> {details}</div></details></div> </div>
+ </div> <div className="row steckbriefbuttonrow" style={{marginTop: "1rem", marginBottom: "1rem"}}> <div className="col-2"> {frontbutton} {backbutton}</div> <div className="col"><details className={frontbriefclass} ><summary> <b>Personal motivation and challenges</b> </summary><div> {details}</div></details></div> </div>
</div>
let whole = <div className={"steckbrief-box"} id={thename}> {hole} </div>;
briefe.push(whole);
@@ -223,7 +226,7 @@ function createPiSteckbriefe(data: Array<SteckbriefInterface>){
<div className="col-4 brieffacts">
<br/><br/> {funfactlist} {facts}
</div>
- </div> <div className="row" style={{marginTop: "1rem", marginBottom: "1rem"}}> <div className="col-2"> {frontbutton} {backbutton}</div> <div className="col"><details className={frontbriefclass} ><summary> <b>Personal motivation and challenges</b> </summary><div> {details}</div></details></div> </div>
+ </div> <div className="row steckbriefbuttonrow" style={{marginTop: "1rem", marginBottom: "1rem"}}> <div className="col-2"> {frontbutton} {backbutton}</div> <div className="col"><details className={frontbriefclass} ><summary> <b>Personal motivation and challenges</b> </summary><div> {details}</div></details></div> </div>
</div>
let whole = <div className={"steckbrief-box"} id={thename}> {hole} </div>;
briefe.push(whole);
diff --git a/src/data/hptimelinedata.tsx b/src/data/hptimelinedata.tsx
index e1ee5a8ed45fa2ce48ceed8f98a3db3e9690598d..e10bebb1c7a546c010983b8955745cb69f84ce34 100644
--- a/src/data/hptimelinedata.tsx
+++ b/src/data/hptimelinedata.tsx
@@ -29,6 +29,8 @@ export interface TimelineDatenpunkt {
references?: Array<React.ReactNode>; /* Muss HTML Code sein - Liliana erstellt den aus Bib dateien */
interview?: React.ReactNode;
text?: string | Array<string> | Array<React.ReactNode>; /* Extra Text */
+ experton?: string;
+ summary: string;
}
type StakeholderTag = 'Industry' | 'Academia' | 'Patient' | 'Medical Professional' | 'Milestone' | 'Other';
@@ -52,6 +54,11 @@ const pics: { [key: string]: string } = {
winkeljann: "https://static.igem.wiki/teams/5247/photos/hp/rnhale-winkeljann.jpg",
kuehnel: "https://static.igem.wiki/teams/5247/photos/hp/hp-philippk-hnel.jpeg ",
wischmeyer: "https://static.igem.wiki/teams/5247/photos/hp/wischmeyer-erhard.webp",
+ nicole: "https://static.igem.wiki/teams/5247/photos/hp/hp-friedlein-nicole.jpg",
+ joshua: "https://static.igem.wiki/teams/5247/photos/hp/joshua.jpg",
+ hammer: "https://static.igem.wiki/teams/5247/photos/hp/hp-hammer.webp",
+ johannfunke: "https://static.igem.wiki/teams/5247/photos/hp/hp-michaeljohannfunke.webp",
+ kühnel: "https://static.igem.wiki/teams/5247/photos/hp/hp-philippk-hnel.jpeg ",
};
/* {
@@ -77,7 +84,7 @@ const pics: { [key: string]: string } = {
export const timelinedata: Array<TimelineDatenpunkt> = [
{
vorname: "Building the team",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
heading: "Development of a multidisciplinary team structure",
@@ -87,11 +94,12 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
{
vorname: "Pitching ideas",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
heading: "Getting Acquainted with Cystic Fibrosis",
@@ -101,11 +109,12 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
{
vorname: "Ideation",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
heading: "Brainstorming and selection of ideas and concepts",
@@ -115,12 +124,13 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
- {
+ {
title: "Prof. Dr.",
vorname: "Kristian",
- nachnname: "Müller",
+ nachnname: "Müller",
job: "Research Group Cellular and Molecular Biotechnology",
affiliation: "Technical Faculty of Bielefeld University",
pictureurl: pics['kristian'],
@@ -133,10 +143,11 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "X",
insights: "X",
implementation: "X",
+ summary: ""
},
- {
+ {
vorname: "Max",
- nachnname: "Beckmann",
+ nachnname: "Beckmann",
job: "Bielefeld University",
affiliation: "Patient and Student of Bielefeld University",
pictureurl: pics['max'],
@@ -149,96 +160,111 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: [<p>When cystic fibrosis came up as a possible topic, we reached out to a teammate's friend Max in the hopes of getting insights into the needs of CF patients and current treatments to verify the need for further treatment options.
Since he was much more enthusiastic and open for discussion than we dared to hope, we extended our exchanges into the realms of the reality of life for CF patients, possible progressions, organizations and doctors in our area and his personal perspectives and values.
The interest in meeting him grew in the whole team and we invited him to one of our meetings. </p>],
- insights: [ <><p>His honest and open answers to us, mostly nothing more than strangers to him, were touching and let the seriousness of cystic fibrosis set in.
- Learning about the challenges he faced felt heavy, besides him being in relatively good health and having a good life quality for a CF patient.
+ insights: [<><p>His honest and open answers to us, mostly nothing more than strangers to him, were touching and let the seriousness of cystic fibrosis set in.
+ Learning about the challenges he faced felt heavy, besides him being in relatively good health and having a good life quality for a CF patient.
</p>
- <p>Additional to the interpersonal effects of our discussion, Max gave us the reasons to continue with gene therapy approach while focusing on the lung:
- Modulators do not erase all symptoms.
- There is a keen interest for new treatments in the CF community.
- The the decreasing lung functionality it the most limiting.
- The immense impact of treatments on the life quality. </p>
- <p>We learned a lot of new things that we did not consider before about cystic fibrosis such as:
- The need for a calorie rich diet and digestive problems.
- The frequency of checkups needed.
- How vastly different the progressions can be.
- The increased need for hygiene to prevent infections.
- The high price of medicines and induvial therapeutics. </p>
- <p>Afterwards, we reflected on the discussion and asked our team members what stuck with them:
- “How much attention has to be paid to everything in everyday life, I hadn't even thought about problems at the hairdresser.â€
- “Simply that he was there and reported everything in such detail. From minute 1, I had permanent goosebumps because I was so moved by this story. I think it's great how he stands his ground in life, does what he wants to do and what defines him as a person. It didn't seem as if his life was determined by CF. I somehow expected it to be different, even if that sounds a bit silly.â€
- “The amount of medication and how expensive it is.â€
- "The statement that left the biggest impression for me was when Max was telling about a friend of his and fellow cystic fibrosis patient who caught a fungi infection which he now cannot get rid of anymore, showing how fast a seemingly little infection can change the life of a cystic fibrosis patient for the worse without any kind of warning.â€
- “The variance in the extent of the limitations of the disease in different patients, including how the disease differs in its severity, even in patients of the same age.â€
- “How positively and calmly Max deals with his illness but has also pointed out that he is lucky, and that other people are much worse off - how much you have to pay attention to little things that you wouldn't have expected as a healthy person.†</p>
- </>],
+ <p>Additional to the interpersonal effects of our discussion, Max gave us the reasons to continue with gene therapy approach while focusing on the lung:
+ Modulators do not erase all symptoms.
+ There is a keen interest for new treatments in the CF community.
+ The the decreasing lung functionality it the most limiting.
+ The immense impact of treatments on the life quality. </p>
+ <p>We learned a lot of new things that we did not consider before about cystic fibrosis such as:
+ The need for a calorie rich diet and digestive problems.
+ The frequency of checkups needed.
+ How vastly different the progressions can be.
+ The increased need for hygiene to prevent infections.
+ The high price of medicines and induvial therapeutics. </p>
+ <p>Afterwards, we reflected on the discussion and asked our team members what stuck with them:
+ “How much attention has to be paid to everything in everyday life, I hadn't even thought about problems at the hairdresser.â€
+ “Simply that he was there and reported everything in such detail. From minute 1, I had permanent goosebumps because I was so moved by this story. I think it's great how he stands his ground in life, does what he wants to do and what defines him as a person. It didn't seem as if his life was determined by CF. I somehow expected it to be different, even if that sounds a bit silly.â€
+ “The amount of medication and how expensive it is.â€
+ "The statement that left the biggest impression for me was when Max was telling about a friend of his and fellow cystic fibrosis patient who caught a fungi infection which he now cannot get rid of anymore, showing how fast a seemingly little infection can change the life of a cystic fibrosis patient for the worse without any kind of warning.â€
+ “The variance in the extent of the limitations of the disease in different patients, including how the disease differs in its severity, even in patients of the same age.â€
+ “How positively and calmly Max deals with his illness but has also pointed out that he is lucky, and that other people are much worse off - how much you have to pay attention to little things that you wouldn't have expected as a healthy person.†</p>
+ </>],
implementation: [<> <p>This most important aspect of this meeting was less an insight, but the fact Max helped us to put a face to an abstract idea. Many of our ideas were interesting and adventurous but meeting him put a lot into perspective. </p>
<p>Our focus shifted to the safety of our creation. When coming up with ideas, we asked ourselves,
Is this idea a promising or an interesting one?
Would it be thrilling to create or benefit patients? </p>
- <p>Due to this, Max had a profound influence on our project from the beginning and is the main reason why we chose Integrated Human Practices and Safety & Security as our special prizes. Only after this discussion did we decide on targeting the lung instead of the pancreas and discarded the idea of a diagnostic approach. He did not only give us important information but most importantly personal investment into our project. </p></>],
+ <p>Due to this, Max had a profound influence on our project from the beginning and is the main reason why we chose Integrated Human Practices and Safety & Security as our special prizes. Only after this discussion did we decide on targeting the lung instead of the pancreas and discarded the idea of a diagnostic approach. He did not only give us important information but most importantly personal investment into our project. </p></>],
pictureurl_implementation: "",
- interview:<><QaBox q="How and when were you first diagnosed? " a="When I was about one year old. My mother did not do any screenings or prenatal testing. I was in pain but as an infant you cannot say that, so I screamed a lot. Many doctors shrug that off in small children but after some time a sweat test was done at the children's clinic."/>
- <QaBox q="What do you think about diagnosing via sweat tests?" a="I am a clear opponent of diagnosing via sweat tests, especially if it is used to rule out CF and people have atypical CF, because of which they do not get diagnosed because of that."/>
- <QaBox q="What symptoms do you have?" a="Before taking modulators, I was underweight and did not feel hunger. I also had no sense of taste. Now, I have a healthy weight and still have respiratory symptoms such as very sticky mucus and digestive issues."/>
- <QaBox q="You are taking individual meds, correct? They are individual in respect to the mutation, not the person, right?" a="Yes, and yes, I am. "/>
- <QaBox q="What other medications are you taking? " a="Nasal spray, pancreatic enzymes, saline solution for inhalation and pantoprazole, used to reduce stomach acid production. "/>
- <QaBox q="Do you know how exactly they work?" a="Yes, I wrote a report on that during school. In the children's clinic they explained it like this: The CFTR channel is like a door and people with CF don’t have that many doors and some of the doors are broken. The medication makes more doors that function."/>
- <QaBox q="What changed when you started taking the modulators? " a="Everything. Most of symptoms are minor now and I have a better lung function and quality of life. I even grew taller."/>
- <QaBox q="Did you formerly take other medication?" a="I don’t remember anything like that, but I also always had good medical care. "/>
- <QaBox q="Do you experience any side effects from your medications?" a="At first yes, a lot. Stomach cramps and difficulty breathing for example."/>
- <QaBox q="Is diabetes a concern of yours?" a="Yes, it is common. I have to go to a diabetes checkup once a year. That happens together with all the other checkups like sonographies."/>
- <QaBox q="Do you know fellow patients that took part in clinical study for gene therapy or at least thought about doing so?" a="I know no one that took part in one but definitely people who would like to do so."/>
- <QaBox q="Do you know other patients that would want to use gene therapy?" a="Yes, most definitely."/>
- <QaBox q="Since your sweat is different, do you have trouble with your temperature regulation?" a="No and I do not know any patients with an issue like that. But it still is uncomfortable in the summer, because the sweat is thick, and it can smell stronger, too."/>
- <QaBox q="How many hours a day are devoted to your illness?" a="Good question, but wrong patient. I am blessed with good health while other people my age may have to be on a ventilator. I currently only have to inhale for 20 minutes every day, take my medication and be conscious about hygiene. I would say 30 minutes a day. "/>
- <QaBox q="That means you do not have many limitations due to CF, is that right?" a="Yes. There are many things I am concerned about but often there is not a different way."/>
- <QaBox q="What are some of the limitations you do have?" a="Of course, I am still concerned about my health and using public bathrooms for example. And I still do not go swimming in lakes and things like that. But all in all, I feel like I can live a very normal life. "/>
- <QaBox q="One concern is hygiene. Our university for example does not have toilet seats in most bathrooms. Do you think there should be?" a="That does not concern healthy people, who are the majority. But specifically for CF-people? No, there are too few at the university. It would be more hygienic overall, though. A “CF-toilet†would be nice as a form of a disabled bathroom."/>
- <QaBox q="How was your childhood as a sick child and how did your parents act with you? " a="My mother is active in the Muko e.V. and has been for some time. My parents always lead by example about what to do and not to do and dealt with it in a good way. My mother was always very committed and involved in giving me good care. I always knew about my illness but felt it was not that bad, because I received good care and education about my illness."/>
- <QaBox q="What is a typical age for a diagnosis in your experience?" a="Somewhere between the pregnancy and one year. It is obvious if the children do not gain weight and there are genetic screenings one can do prenatally or after birth. "/>
- <QaBox q="If a diagnosis is possible during pregnancy, do you know of any treatments during pregnancy?" a="No, I think the youngest age for modulators is 3 years. But people can do genetic testing and counselling before pregnancy."/>
- <QaBox q="What does a high-fat diet entail?" a="For me, it was a lot of oil and butter and high-calory drinks. "/>
- <QaBox q="What would happen if you stopped taking your medications?" a="The first thing to happen would be heavy and dry coughing, because the mucus would not be removed properly anymore. Thus, bacteria would not be properly removed from the lungs anymore either and an infection would become more likely. And I would not be able to really process food anymore, so no nutrients, feeling weak and stomach problems. "/>
- <QaBox q="Physical therapy is a part of your treatment – what exactly do you do there? " a="Breathing exercises and training my lung volume to keep it on the same level. "/>
- <QaBox q="Do you have further wished for your therapy?" a="Not really. I am very lucky and am free of heavy symptoms on most days. "/>
- <QaBox q="Is that the norm or do you know people who do want new therapies?" a="No, there is a need for new therapies. "/>
- <QaBox q="Are these people with different mutations or worse health? " a="I don’t know, the progression is so individual, and infections can create big changes. "/>
- <QaBox q="A therapy for which organ would benefit most people that have worse health than you do?" a="Probably the lung. The pancreas is important too, but stomach problems are usually less pressing than difficulty in breathing."/>
- <QaBox q="You mentioned that doing sport is difficult with CF, why?" a="Hygiene. In the lockers and the showers but also with the equipment."/>
- <QaBox q="Do you feel restricted in your free time activities?" a="No, I always had good alternatives. For example, going swimming at an open-air swimming pool instead of a lake. "/>
- <QaBox q="Would you have more freedom when you are better protected from Pseudomonas spcc. and other potential infections? " a="text"/>
- <QaBox q="text" a="Definitely. That is a big increase in the quality of life and that is a win. It also changes the picture people have of the illness. Of course being protected by prevention is good already but effective therapies for infections increase the sense of freedom even more. "/>
- <QaBox q="You said you are afraid every time you must go for a swab, why is that? " a="I am afraid of getting an infection. That still could be a death sentence. "/>
- <QaBox q="Are rooms with air conditioning a problem due to the possible germs in the air conditioners? " a="No, there is usually enough movement. But humidifiers are bad because of the pond water. "/>
- <QaBox q="You mentioned going to the hairdresser is problematic. Could you elaborate? " a="There are many possible sources of ponding water and with that, infections. That and the hygiene aspect in general. I am visited by my hairdresser, and he only uses a specific spray bottle to wet my hair that I keep and dry thoroughly between uses."/>
- <QaBox q="Are you the first person in your family that has CF? " a="Yes. But I suspect my father has a light or atypical form because he has suspicious mucus."/>
- <QaBox q="With life expectancies looking better, do many patients want to have biological children?" a="Not all but some. I think some would be interested in a therapy that can be done on the fertilized egg to have a healthy child. "/>
- <QaBox q="Do you know the film “Five feet apart� If so, what do think about it, is it accurate? " a="Yes. It does not paint a wrong picture; their progression is possible."/>
- <QaBox q="Do you think there has to be more effort concerning diagnostics?" a="Early diagnosis is covered by the screenings."/>
- <QaBox q="Since you almost had to sue for your medication, do you know if there are any lawyers specializing in cases like this? " a="No, I don’t. "/>
- <QaBox q="Are most of the other patients you know in good health like you?" a="No. Another boy my age got a fungal infection and does not have long time left to live. "/>
+ interview: <><QaBox q="How and when were you first diagnosed? " a="When I was about one year old. My mother did not do any screenings or prenatal testing. I was in pain but as an infant you cannot say that, so I screamed a lot. Many doctors shrug that off in small children but after some time a sweat test was done at the children's clinic." />
+ <QaBox q="What do you think about diagnosing via sweat tests?" a="I am a clear opponent of diagnosing via sweat tests, especially if it is used to rule out CF and people have atypical CF, because of which they do not get diagnosed because of that." />
+ <QaBox q="What symptoms do you have?" a="Before taking modulators, I was underweight and did not feel hunger. I also had no sense of taste. Now, I have a healthy weight and still have respiratory symptoms such as very sticky mucus and digestive issues." />
+ <QaBox q="You are taking individual meds, correct? They are individual in respect to the mutation, not the person, right?" a="Yes, and yes, I am. " />
+ <QaBox q="What other medications are you taking? " a="Nasal spray, pancreatic enzymes, saline solution for inhalation and pantoprazole, used to reduce stomach acid production. " />
+ <QaBox q="Do you know how exactly they work?" a="Yes, I wrote a report on that during school. In the children's clinic they explained it like this: The CFTR channel is like a door and people with CF don’t have that many doors and some of the doors are broken. The medication makes more doors that function." />
+ <QaBox q="What changed when you started taking the modulators? " a="Everything. Most of symptoms are minor now and I have a better lung function and quality of life. I even grew taller." />
+ <QaBox q="Did you formerly take other medication?" a="I don’t remember anything like that, but I also always had good medical care. " />
+ <QaBox q="Do you experience any side effects from your medications?" a="At first yes, a lot. Stomach cramps and difficulty breathing for example." />
+ <QaBox q="Is diabetes a concern of yours?" a="Yes, it is common. I have to go to a diabetes checkup once a year. That happens together with all the other checkups like sonographies." />
+ <QaBox q="Do you know fellow patients that took part in clinical study for gene therapy or at least thought about doing so?" a="I know no one that took part in one but definitely people who would like to do so." />
+ <QaBox q="Do you know other patients that would want to use gene therapy?" a="Yes, most definitely." />
+ <QaBox q="Since your sweat is different, do you have trouble with your temperature regulation?" a="No and I do not know any patients with an issue like that. But it still is uncomfortable in the summer, because the sweat is thick, and it can smell stronger, too." />
+ <QaBox q="How many hours a day are devoted to your illness?" a="Good question, but wrong patient. I am blessed with good health while other people my age may have to be on a ventilator. I currently only have to inhale for 20 minutes every day, take my medication and be conscious about hygiene. I would say 30 minutes a day. " />
+ <QaBox q="That means you do not have many limitations due to CF, is that right?" a="Yes. There are many things I am concerned about but often there is not a different way." />
+ <QaBox q="What are some of the limitations you do have?" a="Of course, I am still concerned about my health and using public bathrooms for example. And I still do not go swimming in lakes and things like that. But all in all, I feel like I can live a very normal life. " />
+ <QaBox q="One concern is hygiene. Our university for example does not have toilet seats in most bathrooms. Do you think there should be?" a="That does not concern healthy people, who are the majority. But specifically for CF-people? No, there are too few at the university. It would be more hygienic overall, though. A “CF-toilet†would be nice as a form of a disabled bathroom." />
+ <QaBox q="How was your childhood as a sick child and how did your parents act with you? " a="My mother is active in the Muko e.V. and has been for some time. My parents always lead by example about what to do and not to do and dealt with it in a good way. My mother was always very committed and involved in giving me good care. I always knew about my illness but felt it was not that bad, because I received good care and education about my illness." />
+ <QaBox q="What is a typical age for a diagnosis in your experience?" a="Somewhere between the pregnancy and one year. It is obvious if the children do not gain weight and there are genetic screenings one can do prenatally or after birth. " />
+ <QaBox q="If a diagnosis is possible during pregnancy, do you know of any treatments during pregnancy?" a="No, I think the youngest age for modulators is 3 years. But people can do genetic testing and counselling before pregnancy." />
+ <QaBox q="What does a high-fat diet entail?" a="For me, it was a lot of oil and butter and high-calory drinks. " />
+ <QaBox q="What would happen if you stopped taking your medications?" a="The first thing to happen would be heavy and dry coughing, because the mucus would not be removed properly anymore. Thus, bacteria would not be properly removed from the lungs anymore either and an infection would become more likely. And I would not be able to really process food anymore, so no nutrients, feeling weak and stomach problems. " />
+ <QaBox q="Physical therapy is a part of your treatment – what exactly do you do there? " a="Breathing exercises and training my lung volume to keep it on the same level. " />
+ <QaBox q="Do you have further wished for your therapy?" a="Not really. I am very lucky and am free of heavy symptoms on most days. " />
+ <QaBox q="Is that the norm or do you know people who do want new therapies?" a="No, there is a need for new therapies. " />
+ <QaBox q="Are these people with different mutations or worse health? " a="I don’t know, the progression is so individual, and infections can create big changes. " />
+ <QaBox q="A therapy for which organ would benefit most people that have worse health than you do?" a="Probably the lung. The pancreas is important too, but stomach problems are usually less pressing than difficulty in breathing." />
+ <QaBox q="You mentioned that doing sport is difficult with CF, why?" a="Hygiene. In the lockers and the showers but also with the equipment." />
+ <QaBox q="Do you feel restricted in your free time activities?" a="No, I always had good alternatives. For example, going swimming at an open-air swimming pool instead of a lake. " />
+ <QaBox q="Would you have more freedom when you are better protected from Pseudomonas spcc. and other potential infections? " a="text" />
+ <QaBox q="text" a="Definitely. That is a big increase in the quality of life and that is a win. It also changes the picture people have of the illness. Of course being protected by prevention is good already but effective therapies for infections increase the sense of freedom even more. " />
+ <QaBox q="You said you are afraid every time you must go for a swab, why is that? " a="I am afraid of getting an infection. That still could be a death sentence. " />
+ <QaBox q="Are rooms with air conditioning a problem due to the possible germs in the air conditioners? " a="No, there is usually enough movement. But humidifiers are bad because of the pond water. " />
+ <QaBox q="You mentioned going to the hairdresser is problematic. Could you elaborate? " a="There are many possible sources of ponding water and with that, infections. That and the hygiene aspect in general. I am visited by my hairdresser, and he only uses a specific spray bottle to wet my hair that I keep and dry thoroughly between uses." />
+ <QaBox q="Are you the first person in your family that has CF? " a="Yes. But I suspect my father has a light or atypical form because he has suspicious mucus." />
+ <QaBox q="With life expectancies looking better, do many patients want to have biological children?" a="Not all but some. I think some would be interested in a therapy that can be done on the fertilized egg to have a healthy child. " />
+ <QaBox q="Do you know the film “Five feet apart� If so, what do think about it, is it accurate? " a="Yes. It does not paint a wrong picture; their progression is possible." />
+ <QaBox q="Do you think there has to be more effort concerning diagnostics?" a="Early diagnosis is covered by the screenings." />
+ <QaBox q="Since you almost had to sue for your medication, do you know if there are any lawyers specializing in cases like this? " a="No, I don’t. " />
+ <QaBox q="Are most of the other patients you know in good health like you?" a="No. Another boy my age got a fungal infection and does not have long time left to live. " />
</>,
+ summary: ""
},
- {
+ {
title: "Prof. Dr.",
- vorname: "Christoph",
- nachnname: "Weber",
- job: "",
+ vorname: "Wolf-Michael",
+ nachnname: "Weber",
+ job: "Professor ",
+ affiliation: "Univesity Münster",
pictureurl: pics['placeholder'],
tag: "Academia",
- heading: "Feedback Session with Expert",
+ heading: "Feedback Session with Experts",
interviewtabid: "weber",
cardtext: "",
language: "en",
- quote: "",
- aimofcontact: "",
-
- insights: "",
- implementation: "",
+ quote: "x",
+ aimofcontact: [<p>The aim of the interview was to gain expert insights on optimizing the delivery of CFTR-mRNA via lung-targeted lipid nanoparticles (LNPs) for cystic fibrosis (CF) treatment.
+ Specifically, the goal was to explore potential cell targets, challenges in delivery mechanisms, and technical tools for assessing the effectiveness of mRNA therapies like the Ussing chamber system. </p>],
+ insights: [<p>The experts highlighted the potential of targeting ionocytes, given their key role in CFTR expression, but emphasized the difficulty in accessing them due to their basal position in the respiratory epithelium.
+ While Prof. Weber found ionocytes to be an intriguing target, Dr. Große-Onnebrink pointed out that there is still limited understanding of their exact role in CF pathology. Both stressed the challenge of penetrating the
+ mucus barrier in vivo, particularly when using air-liquid interface cultures, and underscored the importance of optimizing particle size to ensure effective delivery to the deeper regions of the lungs.
+ Prof. Weber also emphasized the need to test whether the system can still transfect cells in the presence of mucus. </p>,
+ <p>It was suggested to use the Ussing chamber to assess the effectiveness of the delivery system and therapeutic mRNA, though they noted certain challenges with this technique. We also discussed alternatives like organoids,
+ which offer only indirect measurements of CFTR function, and patch clamping, which, though more precise, is a more complex and expensive method. Additionally, Prof. Weber recommended exploring chitosan-based delivery
+ systems due to their success in his previous work, suggesting they could be a safer alternative to PEG-lipid systems, which had shown issues with cytotoxicity. </p>],
+ implementation: [<p>These insights helped refine our iGEM project in several key ways:
+ <ul>
+ <li>Cell Targeting: We decided to continue exploring ionocytes as a target but acknowledged the technical hurdles involved. We also expanded our focus to include multiple cell types to test different delivery systems. </li>
+ <li>Delivery Systems: We began investigating chitosan-based nanoparticles as a safer alternative to PEG-lipid systems. The suggestion to optimize particle size and delivery for inhalation was also integrated into our design. </li>
+ <li>Experimental Tools: Based on the discussion, we plan to use an Ussing chamber to measure overall CFTR function in different cell types but will also explore organoid-based approaches for preliminary testing. Additionally, we consulted the medical faculty on the possibility of using patch clamping for more detailed measurements of successful transfection and restored CFTR function. </li>
+ </ul>,
+ </p>],
+ summary: ""
},
{
vorname: "Exploring new ideas",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
affiliation: "",
@@ -247,15 +273,16 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
- {
+ {
title: "Dr.",
vorname: "Michaela",
- nachnname: "Bienert",
+ nachnname: "Bienert",
job: " Scientific Sales Representative for Cell Culture Products",
affiliation: "Stemcell",
pictureurl: pics['placeholder'],
@@ -268,10 +295,11 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
+ summary: ""
},
{
vorname: "Looking for expertise",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
heading: "Identifying key experts in cystic fibrosis and prime editing",
@@ -279,14 +307,15 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
{
vorname: "Documenting progress",
- nachnname: "",
+ nachnname: "",
pictureurl: pics['placeholder'],
tag: "Other",
heading: "Tracking progress in expert search and idea development",
@@ -294,14 +323,15 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
- type: "meta"
+ type: "meta",
+ summary: ""
},
{
vorname: "Jan-Phillipp",
- nachnname: "Gerhards",
+ nachnname: "Gerhards",
job: "Student",
affiliation: "Intern at Harvard/ Boston Childrens Hospital",
pictureurl: "https://static.igem.wiki/teams/5247/photos/hp/hp-jpgerhards-potrats.webp",
@@ -310,16 +340,17 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
interviewtabid: "JPpegRNA",
cardtext: "",
language: "de",
- quoteNachname:"Lenger, Teammember",
- quoteVorname:"Malte",
+ quoteNachname: "Lenger, Teammember",
+ quoteVorname: "Malte",
quote: "The interview proved invaluable in gaining an initial understanding of the principles of pegRNA design and optimisation, particularly in the context of silent edits.",
aimofcontact: "The aim of the contact was to engage in a discussion about prime editing and pegRNAs, as the Jan-Phillip Gerhards had used these technologies in his internship. We sought to exchange ideas, gather insights, and explore potential improvements or strategies for our project, leveraging his experience with prime editing tools. His practical knowledge in this field was very valuable for refining our approach and ensuring we were aligned with the latest advancements and methodologies in prime editing. ",
insights: "During our discussion we gained valuable insights that had a significant impact on our project. One of the most important findings was the effectiveness of silent edits, which will enable us to make our PrimeGuide safer. Silent edits changes the sequence of bases in the DNA in such a way that the resulting protein remains unchanged, because the genetic code is redundant. This means that different codons can code for the same amino acid. By making silent edits in addition to correcting the CFTR gene, we can prevent the pegRNA from rebinding. We have also learned that the length of the primer binding site (PBS) plays a crucial role in determining optimal results and that it is recommended to keep the PBS temperature close to 37°C. Specifically, PBS lengths of 17nt (38.3°C) and 16nt (36.4°C) were found to be ideal options. For our planned set of 12 samples, it was recommended to use three different PBS lengths (differing by +/- 1nt from that close to 37°C) in combination with four RTTs to achieve the best result. Another important finding was the use of non-annotated regions with overhangs for cloning, which could give better results in our experiments. However, we also encountered concerns that circRNA, a covalently closed circular RNA molecule, might be sterically hindered by Cas9, which we need to investigate further. When discussing cloning overhangs, we learned that a base-pair length close to 60°C is optimal. However, the use of a 15nt PBS was not recommended as it has a lower temperature range which could affect performance. Although we still need to confirm the oligonucleotide delivery time, these findings will help us to refine our cloning strategy, optimise PBS selection and improve our overall approach to primer editing, especially in terms of the pegRNA design.",
implementation: "We incorporated the lessons learned from our discussions on prime editing and silent editing directly into our project by refining our approach to gene editing. Based on feedback about the optimal length of primer binding sequences (PBS) and RTTs, we adjusted the design of our pegRNAs to ensure greater precision and efficiency in our experiments. In particular, we learned that using PBS lengths close to 37°C melting temperatures (e.g. 16-17 nucleotides) increased stability, which led us to fine-tune these sequences for improved editing results. The concept of silent editing became an integral part of our safety strategy, allowing us to make changes to the DNA more precise. We also revised our cloning strategies by considering the appropriate overhang length, targeting a base pair length near the melting temperature of 60°C to improve cloning efficiency. We also reassessed the practicality of ordering shorter PBS sequences, concluding that lengths shorter than 15 nt were less advantageous due to reduced efficiency. By integrating these findings, we optimised our experimental workflow and made informed decisions about the tools and methods for our prime editing experiments. ",
+ summary: ""
},
- {
+ {
vorname: "Katrin",
- nachnname: "Westhoff",
+ nachnname: "Westhoff",
job: "Physiotherapist",
affiliation: "Independent",
pictureurl: pics['westhoff'],
@@ -333,11 +364,12 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
insights: "The interview yielded valuable insights into the regular implementation of the therapy, the use of aids and the adaptation of exercises to the individual needs of the patients. It was notable that the therapy has improved considerably thanks to better medication and adapted exercises, with a concomitant increase in life expectancy for children affected by cystic fibrosis. Of particular interest was the emphasis on the importance of sport and exercise, which should not only be therapeutically effective, but also increase quality of life. ",
implementation: "The following statement by Katrin Westhoff had a particularly profound impact on our project: 'The more we know, the more opportunities we have.' We learned from the interview that the current medication is already helping many patients to a huge extent, but that there is still a significant opportunity for improvement. After all, successful gene therapy would markedly enhance the quality of life for those affected. The findings of this project will be disseminated to the relevant researchers in order to facilitate the rapid improvement of the quality of life of all cystic fibrosis patients, regardless of their mutation. ",
pictureurl_interview: "https://static.igem.wiki/teams/5247/photos/hp/katrin-westhoff-zoom.webp",
+ summary: ""
},
- {
+ {
title: "Dr.",
vorname: "Cristian-Gabriel",
- nachnname: "Olariu",
+ nachnname: "Olariu",
job: "pediatrician",
affiliation: "OWL University Hospital",
pictureurl: pics['olariu'],
@@ -347,82 +379,82 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
language: "de",
quote: "For most families, it’s a shock. Cystic fibrosis still has a strong association with being a life-threatening disease, despite the fact that we now have good treatments, and many patients can live healthy lives. The diagnosis puts a huge psychological strain on the family, especially when dealing with very young children.",
- aimofcontact: "To gain a deeper insight into the path to diagnosis, we invited pediatrician Dr. Cristian-Gabriel Olariu from the University Department of Pediatrics and Adolescent Medicine to share his experiences with cystic fibrosis (CF) patients with us. We interviewed him because of his expertise in the effects of diagnosis on the patient and the family members, but also on daily life. Additionally, we want to close the gap and create a bridge between academic research and clinical applications. Therefore, Dr. Olariu gave insights about the clinical perspectives on CF patients." ,
+ aimofcontact: "To gain a deeper insight into the path to diagnosis, we invited pediatrician Dr. Cristian-Gabriel Olariu from the University Department of Pediatrics and Adolescent Medicine to share his experiences with cystic fibrosis (CF) patients with us. We interviewed him because of his expertise in the effects of diagnosis on the patient and the family members, but also on daily life. Additionally, we want to close the gap and create a bridge between academic research and clinical applications. Therefore, Dr. Olariu gave insights about the clinical perspectives on CF patients.",
insights: [<p>We invited Max, our CF patient contact, to join Dr. Olariu in discussing the intersection of academic research, clinical application, and patient needs. Through our connection with CF Vests Worldwide (link zu deren Website? https://www.cfvww.org), an organization dedicated to providing life-saving therapy vests to cystic fibrosis patients globally, we gained insights into the challenges faced by CF patients, particularly in regions like Thailand, where access to advanced treatments and medical devices is limited. The conversation highlighted the critical role of early diagnosis and intervention, as well as the quality-of-life challenges many patients endure due to conventional treatments that may not be effective for everyone. Innovative approaches, such as our SORT LNP (lipid nanoparticle) delivery system, present promising alternatives for CF therapy. This system, which allows for RNA encapsulation and administration via dry spray inhalation, could revolutionize treatment by targeting lung cells more effectively, particularly in resource-limited settings. Dr. Olariu underscored the need for psychological support and coordinated care for CF patients, emphasizing that novel therapies like LNP-based gene treatments have the potential to improve treatment efficacy and accessibility, ultimately reducing the lifelong burden of care for patients and their families. </p>,
- <ol>
- <li>Diagnosis:</li>
- <li>Detection through newborn screening.</li>
- <li>Further tests (including sweat tests) are conducted if results are abnormal.</li>
- </ol>,
+ <ol>
+ <li>Diagnosis:</li>
+ <li>Detection through newborn screening.</li>
+ <li>Further tests (including sweat tests) are conducted if results are abnormal.</li>
+ </ol>,
- <ol>
- <li>Early Treatment:</li>
- <li>Begins with inhalations, physiotherapy, and medications.</li>
- <li>Aim: Prevention of severe complications and organ protection.</li>
- </ol>,
+ <ol>
+ <li>Early Treatment:</li>
+ <li>Begins with inhalations, physiotherapy, and medications.</li>
+ <li>Aim: Prevention of severe complications and organ protection.</li>
+ </ol>,
+
+ <ol>
+ <li>Challenges:</li>
+ <li>Some patients do not respond well to conventional treatments.</li>
+ <li>Significantly impacts quality of life.</li>
+ </ol>,
- <ol>
- <li>Challenges:</li>
- <li>Some patients do not respond well to conventional treatments.</li>
- <li>Significantly impacts quality of life.</li>
- </ol>,
+ <ol>
+ <li>Family Burden:</li>
+ <li>Medical challenges create a significant burden.</li>
+ <li>Psychological stress due to lifelong treatment.</li>
+ </ol>,
- <ol>
- <li>Family Burden:</li>
- <li>Medical challenges create a significant burden.</li>
- <li>Psychological stress due to lifelong treatment.</li>
- </ol>,
+ <ol>
+ <li>Importance of Support: </li>
+ <li>Psychological support is crucial.</li>
+ <li>A well-functioning treatment team is essential.</li>
+ </ol>,
+ <p>We have jointly weighed up the extent to which an early diagnosis is always an advantage, as some parents perceive an early diagnosis as an additional burden and would prefer to experience the first years of their child's life without constant medical intervention. Especially when there are cases in which patients only show a clear clinical picture at an advanced age. The psychological burden also lies with the children, who often experience medical trauma because they are involved in such intensive medical care from birth. Additionally, the treatment of cystic fibrosis is very expensive, and the costs are covered by health insurance companies to varying degrees. In some countries, such as the USA, Ukraine or Developing countries, many families cannot afford the necessary treatments. Dr Olariu drew our attention to another problem in the treatment of cystic fibrosis. Infections, especially with bacteria such as Pseudomonas spcc., are difficult to treat and often lead to long hospital stays. Max, our patients’ representative, who knows Dr. Olariu through his treatment, talked about his infections with Pseudomonas spcc., illustrating the reality of an invisible danger that determines a patient's everyday life. Strict hygiene measures are required to prevent infections, such as wearing face masks in hospital and careful handling of potential sources of infection. The clinics where cystic fibrosis patients are treated work closely with a multidisciplinary team of doctors, psychologists, physiotherapists and nutritionists to ensure that patients receive holistic care. At the same time, research is constantly being carried out and new therapeutic approaches developed, such as the use of nanoparticles to improve drug delivery. Former patients are also involved in research and provide valuable insights and advances. </p>,
+ <ol>
+ <li>Pros of Early Diagnosis and Treatment</li> </ol>,
+ <ol>
+ <li>Timely Intervention: Prevents severe organ damage and improves long-term outcomes.</li>
+ <li>Holistic Care: Involves a multidisciplinary team for comprehensive patient support.</li>
+ <li>Access to Innovations: Allows patients to benefit from advancements like nanoparticle drug delivery.</li>
+ <li>Family Support: Provides education and resources for effective management from the start.</li>
+ </ol>,
- <ol>
- <li>Importance of Support: </li>
- <li>Psychological support is crucial.</li>
- <li>A well-functioning treatment team is essential.</li>
- </ol>,
- <p>We have jointly weighed up the extent to which an early diagnosis is always an advantage, as some parents perceive an early diagnosis as an additional burden and would prefer to experience the first years of their child's life without constant medical intervention. Especially when there are cases in which patients only show a clear clinical picture at an advanced age. The psychological burden also lies with the children, who often experience medical trauma because they are involved in such intensive medical care from birth. Additionally, the treatment of cystic fibrosis is very expensive, and the costs are covered by health insurance companies to varying degrees. In some countries, such as the USA, Ukraine or Developing countries, many families cannot afford the necessary treatments. Dr Olariu drew our attention to another problem in the treatment of cystic fibrosis. Infections, especially with bacteria such as Pseudomonas spcc., are difficult to treat and often lead to long hospital stays. Max, our patients’ representative, who knows Dr. Olariu through his treatment, talked about his infections with Pseudomonas spcc., illustrating the reality of an invisible danger that determines a patient's everyday life. Strict hygiene measures are required to prevent infections, such as wearing face masks in hospital and careful handling of potential sources of infection. The clinics where cystic fibrosis patients are treated work closely with a multidisciplinary team of doctors, psychologists, physiotherapists and nutritionists to ensure that patients receive holistic care. At the same time, research is constantly being carried out and new therapeutic approaches developed, such as the use of nanoparticles to improve drug delivery. Former patients are also involved in research and provide valuable insights and advances. </p>,
- <ol>
- <li>Pros of Early Diagnosis and Treatment</li> </ol>,
- <ol>
- <li>Timely Intervention: Prevents severe organ damage and improves long-term outcomes.</li>
- <li>Holistic Care: Involves a multidisciplinary team for comprehensive patient support.</li>
- <li>Access to Innovations: Allows patients to benefit from advancements like nanoparticle drug delivery.</li>
- <li>Family Support: Provides education and resources for effective management from the start.</li>
- </ol>,
-
<ol>
- <li>Cons of Early Diagnosis and Treatment</li></ol>,
- <ol>
- <li>Psychological Burden: May cause stress for parents and children due to constant medical interventions.</li>
- <li>Cost Implications: Treatments can be expensive, with varying insurance coverage, leaving many families unable to afford care.</li>
- <li>Infection Risks: Patients still face risks from infections like Pseudomonas spp., leading to potential hospitalizations.</li>
- <li>Over-medicalization: Continuous focus on treatment can overwhelm families, affecting the quality of early childhood experiences.</li>
- </ol>,
- ],
+ <li>Cons of Early Diagnosis and Treatment</li></ol>,
+ <ol>
+ <li>Psychological Burden: May cause stress for parents and children due to constant medical interventions.</li>
+ <li>Cost Implications: Treatments can be expensive, with varying insurance coverage, leaving many families unable to afford care.</li>
+ <li>Infection Risks: Patients still face risks from infections like Pseudomonas spp., leading to potential hospitalizations.</li>
+ <li>Over-medicalization: Continuous focus on treatment can overwhelm families, affecting the quality of early childhood experiences.</li>
+ </ol>,
+ ],
implementation: "In summary, our project greatly benefited from the conversation with Dr. Olariu. His insights into the complexities of cystic fibrosis treatment, particularly the significance of early diagnosis, were invaluable. Max’s personal experiences added a crucial human perspective, illustrating the medical and psychological challenges he faces, including infections with Pseudomonas spp. Dr. Olariu emphasized the importance of a multidisciplinary approach, involving not just medical professionals but also psychologists, physiotherapists, and nutritionists for holistic care. This discussion helped us appreciate the balance between timely interventions and the emotional burden on patients and their families, guiding us to develop a more empathetic understanding of living with cystic fibrosis. ",
interview: <>
- <QaBox q="Could you please tell us about the journey that parents go through with their CF-sick children from the first visit to diagnosis and treatment?" a="Since 2016, cystic fibrosis (CF) diagnosis has been part of newborn screening. This means that we receive many children right after birth whose screening results were abnormal. These children are then sent to us for further clarification. Not every child with an abnormal screening result is sick, so we perform a sweat test, and about one-third of the children are diagnosed with the disease. The advantage of early diagnosis is that we can intervene and start treatment early to prevent organ damage. However, there are also rare mutations where the course of the disease is difficult to predict." />
- <QaBox q="What are the pros and cons of newborn screening for cystic fibrosis?" a="From a medical point of view, it’s beneficial that we can catch many of these cases early, allowing us to act swiftly. There are even medications for small babies, and early intervention can protect organs, preventing conditions that would require transplants later on. On the downside, because of the wide variety of genetic mutations, some cases we identify may not show significant symptoms until adulthood. This creates a dilemma, as we can’t predict how their condition will progress, but we still start treatments early, which can be stressful for families." />
- <QaBox q="Can you give us an example of how this stress impacts families?" a="Yes, I’ve been caring for a patient from birth who is now five years old and doing very well. However, from the beginning, she had to undergo physiotherapy, regular check-ups, and blood tests, even though she hasn’t shown any major symptoms. Her mother once told me she wasn't sure if she would make the same decision again, as the early intervention caused a lot of stress. She wondered if she might have enjoyed the first year of her child’s life more if things had been more relaxed. Now, at age five, nothing significant has changed in her condition, and they’ve decided against starting modulator therapy for the time being." />
- <QaBox q="How do families typically react when a CF diagnosis is confirmed?" a="For most families, it’s a shock. Cystic fibrosis still has a strong association with being a life-threatening disease, despite the fact that we now have good treatments and many patients can live healthy lives. The diagnosis puts a huge psychological strain on the family, especially when dealing with very young children. The most important factor in managing this, aside from medical treatments, is the support from the medical team. It’s critical to have a team that works well together, not just a single doctor calling all the shots. Families often need much more psychological and nutritional support early on than medical intervention, and this is where having a multidisciplinary team becomes essential." />
- <QaBox q="What is the process for diagnosing and treating older patients who haven’t been through newborn screening?" a="Older patients who come to us with complaints may not have undergone newborn screening, so they are diagnosed based on their symptoms. These complaints can range from mild to severe and are often non-specific, like chronic cough or failure to thrive. When the cause of these symptoms isn’t immediately clear, we do a sweat test. Once diagnosed, we can start treatment, which often involves working with a psychologist to help the family process the news." />
- <QaBox q="How do you support families during the initial shock of diagnosis?" a="When the diagnosis is particularly difficult for families to process, we sometimes have the patients stay in the hospital for up to a week. This gives us time to meet with them daily, answer questions, and provide guidance. During the first consultation, families often fall into a state of shock, and no matter how carefully the doctor explains things, it’s hard for them to absorb all the information. Meeting with them again over the following days helps, and we have specialists in hygiene, physiotherapy, and social counseling on the team to offer holistic support." />
- <QaBox q="What happens if a child gets infected with Pseudomonas or another bacterial culture in the lungs?" a="Pseudomonas is one of the most feared infections for CF patients. It’s a common environmental bacterium that is difficult for CF patients to clear from their lungs. Once we detect it, we treat the patient with specific antibiotics, often through intravenous delivery over two weeks in the hospital. After the initial treatment, patients may continue with inhaled antibiotics for several months to prevent further infection. It’s a very intensive process, taking a lot of time and energy, and even though we may get rid of the infection a few times, eventually the germ can become resistant and stay in the body." />
- <QaBox q="Are there any preventative measures to avoid Pseudomonas infection?" a="Yes, there are hygiene measures. For example, CF patients always wear masks in the hospital to avoid infection from other patients. But it’s difficult to avoid Pseudomonas entirely since it’s found in stagnant water and other places in the environment. We advise patients to be cautious with water sources like sinks or ponds. However, we need to balance strict hygiene with quality of life, especially for children, as being overly strict can lead to obsessive-compulsive behaviors without necessarily reducing the risk of infection." />
- <QaBox q="Do some families resist the medical advice on preventing infections?" a="On an emotional level, I feel that families who take calculated risks to improve their quality of life tend to cope better. Overprotection can lead to greater psychological stress. However, I don't have enough experience to say for sure whether those who don’t protect themselves as strictly get infected earlier or suffer worse outcomes. It’s also worth noting that new therapies are now available that help reduce infection risks, allowing for a bit more freedom, especially for children." />
- <QaBox q="How often do patients need to be tested for infections like Pseudomonas?" a="The official guideline is every two months, but realistically we aim for every 3-4 months. Regular testing is important because Pseudomonas can be present without symptoms. If too much time passes before detection, it becomes harder to remove the infection." />
- <QaBox q="How do you manage chronically infected patients?" a="Patients who are chronically infected with Pseudomonas don't stay in the hospital indefinitely. They usually remain at home, inhaling antibiotics daily and taking physiotherapy to help clear mucus from their lungs. Intravenous antibiotic therapy is reserved for more severe cases or during clinical deterioration." />
- <QaBox q="Are chronically infected patients allowed to visit your practice?" a="Yes, chronically infected patients are allowed to visit the practice. We try to schedule them at different times to avoid contact between infected and non-infected patients, and we often use separate rooms to minimize risk." />
- <QaBox q="How often do children and adults need to have lung function tests?" a="You can’t conduct a good lung function test until the child is around five years old. After that, it becomes part of the routine check-up because it’s non-invasive and provides a good indicator of lung health. We see children every three months, and I believe the protocol is the same for adults." />
- <QaBox q="What do you think about support groups or health retreats for CF patients?" a="Support groups are extremely important. Although we are a good medical team, advice from peers often resonates more with patients. We’ve organized two parents' evenings recently, where parents can exchange experiences and support each other. Unfortunately, we can’t invite the children themselves due to the risk of infection, but in rehabilitation settings, they can meet in germ-specific groups and benefit from shared experiences." />
- <QaBox q="Is there a risk of antibiotic resistance with repeated treatments?" a="Yes, resistance is a concern, especially with repeated antibiotic treatments. However, there’s often a discrepancy between what we see in lab tests and the clinical outcomes. Even if a germ shows resistance on paper, many patients still respond well to treatment. We base our decisions more on clinical outcomes than lab results, changing antibiotics only if the patient’s condition doesn’t improve." />
- <QaBox q="Are there any side effects to the medications?" a="Yes, all medications have potential side effects, though many of them are minor, like rashes or stomachaches. One serious side effect of some antibiotics is hearing damage, which can lead to lifelong hearing loss. This is why we closely monitor patients in the hospital when starting treatments. The newer therapies, like modulators, can cause liver stress, so we regularly check liver enzymes in the blood. However, severe side effects are rare, and the drugs are generally well tolerated." />
+ <QaBox q="Could you please tell us about the journey that parents go through with their CF-sick children from the first visit to diagnosis and treatment?" a="Since 2016, cystic fibrosis (CF) diagnosis has been part of newborn screening. This means that we receive many children right after birth whose screening results were abnormal. These children are then sent to us for further clarification. Not every child with an abnormal screening result is sick, so we perform a sweat test, and about one-third of the children are diagnosed with the disease. The advantage of early diagnosis is that we can intervene and start treatment early to prevent organ damage. However, there are also rare mutations where the course of the disease is difficult to predict." />
+ <QaBox q="What are the pros and cons of newborn screening for cystic fibrosis?" a="From a medical point of view, it’s beneficial that we can catch many of these cases early, allowing us to act swiftly. There are even medications for small babies, and early intervention can protect organs, preventing conditions that would require transplants later on. On the downside, because of the wide variety of genetic mutations, some cases we identify may not show significant symptoms until adulthood. This creates a dilemma, as we can’t predict how their condition will progress, but we still start treatments early, which can be stressful for families." />
+ <QaBox q="Can you give us an example of how this stress impacts families?" a="Yes, I’ve been caring for a patient from birth who is now five years old and doing very well. However, from the beginning, she had to undergo physiotherapy, regular check-ups, and blood tests, even though she hasn’t shown any major symptoms. Her mother once told me she wasn't sure if she would make the same decision again, as the early intervention caused a lot of stress. She wondered if she might have enjoyed the first year of her child’s life more if things had been more relaxed. Now, at age five, nothing significant has changed in her condition, and they’ve decided against starting modulator therapy for the time being." />
+ <QaBox q="How do families typically react when a CF diagnosis is confirmed?" a="For most families, it’s a shock. Cystic fibrosis still has a strong association with being a life-threatening disease, despite the fact that we now have good treatments and many patients can live healthy lives. The diagnosis puts a huge psychological strain on the family, especially when dealing with very young children. The most important factor in managing this, aside from medical treatments, is the support from the medical team. It’s critical to have a team that works well together, not just a single doctor calling all the shots. Families often need much more psychological and nutritional support early on than medical intervention, and this is where having a multidisciplinary team becomes essential." />
+ <QaBox q="What is the process for diagnosing and treating older patients who haven’t been through newborn screening?" a="Older patients who come to us with complaints may not have undergone newborn screening, so they are diagnosed based on their symptoms. These complaints can range from mild to severe and are often non-specific, like chronic cough or failure to thrive. When the cause of these symptoms isn’t immediately clear, we do a sweat test. Once diagnosed, we can start treatment, which often involves working with a psychologist to help the family process the news." />
+ <QaBox q="How do you support families during the initial shock of diagnosis?" a="When the diagnosis is particularly difficult for families to process, we sometimes have the patients stay in the hospital for up to a week. This gives us time to meet with them daily, answer questions, and provide guidance. During the first consultation, families often fall into a state of shock, and no matter how carefully the doctor explains things, it’s hard for them to absorb all the information. Meeting with them again over the following days helps, and we have specialists in hygiene, physiotherapy, and social counseling on the team to offer holistic support." />
+ <QaBox q="What happens if a child gets infected with Pseudomonas or another bacterial culture in the lungs?" a="Pseudomonas is one of the most feared infections for CF patients. It’s a common environmental bacterium that is difficult for CF patients to clear from their lungs. Once we detect it, we treat the patient with specific antibiotics, often through intravenous delivery over two weeks in the hospital. After the initial treatment, patients may continue with inhaled antibiotics for several months to prevent further infection. It’s a very intensive process, taking a lot of time and energy, and even though we may get rid of the infection a few times, eventually the germ can become resistant and stay in the body." />
+ <QaBox q="Are there any preventative measures to avoid Pseudomonas infection?" a="Yes, there are hygiene measures. For example, CF patients always wear masks in the hospital to avoid infection from other patients. But it’s difficult to avoid Pseudomonas entirely since it’s found in stagnant water and other places in the environment. We advise patients to be cautious with water sources like sinks or ponds. However, we need to balance strict hygiene with quality of life, especially for children, as being overly strict can lead to obsessive-compulsive behaviors without necessarily reducing the risk of infection." />
+ <QaBox q="Do some families resist the medical advice on preventing infections?" a="On an emotional level, I feel that families who take calculated risks to improve their quality of life tend to cope better. Overprotection can lead to greater psychological stress. However, I don't have enough experience to say for sure whether those who don’t protect themselves as strictly get infected earlier or suffer worse outcomes. It’s also worth noting that new therapies are now available that help reduce infection risks, allowing for a bit more freedom, especially for children." />
+ <QaBox q="How often do patients need to be tested for infections like Pseudomonas?" a="The official guideline is every two months, but realistically we aim for every 3-4 months. Regular testing is important because Pseudomonas can be present without symptoms. If too much time passes before detection, it becomes harder to remove the infection." />
+ <QaBox q="How do you manage chronically infected patients?" a="Patients who are chronically infected with Pseudomonas don't stay in the hospital indefinitely. They usually remain at home, inhaling antibiotics daily and taking physiotherapy to help clear mucus from their lungs. Intravenous antibiotic therapy is reserved for more severe cases or during clinical deterioration." />
+ <QaBox q="Are chronically infected patients allowed to visit your practice?" a="Yes, chronically infected patients are allowed to visit the practice. We try to schedule them at different times to avoid contact between infected and non-infected patients, and we often use separate rooms to minimize risk." />
+ <QaBox q="How often do children and adults need to have lung function tests?" a="You can’t conduct a good lung function test until the child is around five years old. After that, it becomes part of the routine check-up because it’s non-invasive and provides a good indicator of lung health. We see children every three months, and I believe the protocol is the same for adults." />
+ <QaBox q="What do you think about support groups or health retreats for CF patients?" a="Support groups are extremely important. Although we are a good medical team, advice from peers often resonates more with patients. We’ve organized two parents' evenings recently, where parents can exchange experiences and support each other. Unfortunately, we can’t invite the children themselves due to the risk of infection, but in rehabilitation settings, they can meet in germ-specific groups and benefit from shared experiences." />
+ <QaBox q="Is there a risk of antibiotic resistance with repeated treatments?" a="Yes, resistance is a concern, especially with repeated antibiotic treatments. However, there’s often a discrepancy between what we see in lab tests and the clinical outcomes. Even if a germ shows resistance on paper, many patients still respond well to treatment. We base our decisions more on clinical outcomes than lab results, changing antibiotics only if the patient’s condition doesn’t improve." />
+ <QaBox q="Are there any side effects to the medications?" a="Yes, all medications have potential side effects, though many of them are minor, like rashes or stomachaches. One serious side effect of some antibiotics is hearing damage, which can lead to lifelong hearing loss. This is why we closely monitor patients in the hospital when starting treatments. The newer therapies, like modulators, can cause liver stress, so we regularly check liver enzymes in the blood. However, severe side effects are rare, and the drugs are generally well tolerated." />
</>,
pictureurl_aim: "https://static.igem.wiki/teams/5247/photos/hp/interview-olariu.svg",
pictureurl_interview: "https://static.igem.wiki/teams/5247/photos/hp/olario-abbildung1.svg",
-
+ summary: ""
},
- {
+ {
vorname: "Mattijs",
- nachnname: "Bulcaen",
+ nachnname: "Bulcaen",
job: "PhD Researcher at Laboratory for Molecular Virology & Gene Therapy",
affiliation: "KU Leuven",
pictureurl: pics['mattijs'],
@@ -435,37 +467,37 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: [<p>Shortly after we decided to use prime editing as the gene editing method for our cystic fibrosis therapy, Mattijs Bulcaen from the Laboratory of Molecular Virology and Gene Therapy at KU Leuven and his colleagues published a paper directly related to our research <TabScrollLink tab="mattijsinv" scrollId="desc-1" num="1" />. In contrast to our approach, Bulcaen et al. 2024 targeted other, less common but drug-refractory CFTR-specific mutations (L227R- and N1303K).  </p>],
insights: "The interview with Mattijs was valuable for us in a lot of ways. At that point in the project we were starting to design the components of our prime editor, but we were lacking a broader overview over the state of the field. Mattijs gave us this insight, mentioning techniques like PE3b systems, dsgRNAs and a talk given by David Liu,[Link] the principal investigator behind prime editing that helped us to consider further novel advancements in in Prime Editing and include them into our project. He discussed with us the difficulties that might await us when targeting the CFTR F508del deletion and mentioned that insertions of all the edits possible with prime editing are the hardest to make, the recognition of edits in the region might attract mismatch repair systems and the chromatin organization might negatively impact prime editing efficiency. Also, we learned a lot about how to design our pegRNAs, with important inputs being the 3’ stem loop motif trevopreQ1 used by Mattijs in his publication and the suggestion to use prediction tools to evaluate sgRNA spacer cutting efficiency. We reviewed our approach of testing pegRNAs using the PEAR reporter system and Mattjis recommended to use HEK cell lines for screening because of their easy handling and naturally impaired mismatch repair system. ",
implementation: "The inputs given by Mattijs directly impacted our design choices for multiple parts of the project. For the pegRNA design, we decided to use the same 3’ motif as Mattijs had used and also, like he suggested, checked our spacer candidates for predicted cleavage efficiency. Also we used HEK cells for screening our pegRNAs. We looked further into PE systems that influence cellular mismatch repair (such as PE4) and tried to include these into our design. ",
- interview:<>
- <QaBox q="You mentioned that it was quite challenging to target the F508 delta mutation. Could you provide more detailed reasons for why this is the case or explain why this mutation is particularly difficult to target compared to others?" a="Yes, that's the million-dollar question. First of all, let me clarify: our group has never directly worked on that mutation because we immediately focused on the drug-refractory mutations, such as nonsense mutations where the protein is not formed, indel mutations, or severe missense mutations that do not respond to modulator therapies. Of course, we know several groups in the field who either work on gene editing or focus on cystic fibrosis (CF). We've heard from some of them who attempted to target the F508 delta mutation. For example, some collaborators really tried to design different guides but were unable to find anything above the detection limit. F508del is probably one of the most logical mutations to try to correct, not just for CF but for the entire gene-editing field. If you look at the frequencies of mutations that cause genetic diseases, the F508 delta mutation is by far the most common deletion mutation causing a severe disease. This is because CF, along with sickle cell disease, is one of the most common deadly inherited diseases, and it's overrepresented within CF. So, it makes sense that they would have been trying to target it from the beginning. Interestingly, if you read the Prime Editing paper by Anzalone, F508 delta is mentioned in the introduction in connection with cystic fibrosis. So, it's somewhat surprising that after all this time—it's been almost five years now—they haven't published or released anything on F508 delta. However, last weekend, there was an online seminar where David Liu gave a talk, and he showed some unpublished data indicating that they managed to achieve quite good Prime Editing efficiency on F508 delta. It's worth noting that David Liu rarely presents unpublished data unless the publication is either accepted or very close to acceptance. So, we all kind of expect that the paper will be published soon, perhaps within the next week or at least within a month. From what I saw, it appears they leveraged many of the approaches available today to enhance Prime Editing. Now, regarding your question about why this mutation is so difficult to target with Prime Editing, I can't provide an exact answer. However, I can list some potential difficulties associated with the mutation, and it’s likely that F508 delta is challenging for several of these reasons. For instance, it could be related to the genomic region itself. Writing insertions can be more difficult; the easiest edits are single-point mutations, followed by deletions, and the most challenging are insertions. This difficulty arises because it involves writing a third strand and then relying on DNA damage repair mechanisms to fix it. It could also be that the region around the F508 delta mutation is challenging due to flap equilibration or that it attracts pathways such as mismatch repair that negatively impact Prime Editing. Additionally, the chromatin organization around that region could play a role. Over the past year, we’ve gathered clues that chromatin organization significantly affects Prime Editing capability, while this is much less of an issue for Cas9 and base editors. Studying this is not straightforward; you would need to conduct experiments like ATAC-seq to determine the chromatin organization around the mutation and how it might interfere. I also noticed on a slide that dsgRNAs were mentioned, though David Liu didn't discuss them in his talk. After looking them up online, I found that this technique, published a few years ago by other researchers, is specifically designed to open up chromatin. It seems they use different guides, without the three-prime extension, to open up the chromatin, which could be one way to overcome the limitations in Prime Editing efficiency. There could be other factors as well, and it’s often difficult to predict what will work and what won't. We have prediction tools for Prime Editing guides that work to some extent, but they are not as effective as the prediction tools available for regular CRISPR guide RNAs. This suggests that the Prime Editing system is more complex than the canonical CRISPR systems, with more variables that can influence success or failure. I hope this answers your question somewhat." />
- <QaBox q="Perhaps we could quickly discuss which part of the prime editing complex you think plays the most significant role in making insertions much more challenging compared to deletions. Is it the reverse transcriptase or the RNA?" a="I don't think it's primarily the reverse transcriptase that's the issue. People have shown that longer insertions are definitely possible. I believe the challenge lies in the process when your cell has to repair the new DNA strand, which is generated and exists as a three-stranded intermediate. We don’t directly intervene in this process; it entirely depends on the cell and the DNA damage repair pathways active in those cells. Through expression of dominant negative DNA damage repair effectors, or by nicking the non-edited strand, the outcome can be steered to some extent. When you perform an insertion, the new strand must hybridize with the bottom strand, which remains intact. This creates a small loop that needs to be incorporated. At this point, the cell faces two options: it can either revert to the original state or incorporate the edit you’re trying to introduce. In certain circumstances, perhaps due to how the new DNA strand folds or the sequence context of the region of interest, the cell might heavily favor reverting to the original state, resulting in the absence of the intended edit. This process is extremely difficult to predict, but there are several indications pointing in this direction. For example, in the case of point mutations, it has been shown that it’s easier to convert a C to a G rather than the reverse, simply due to how these mismatches are recognized by the DNA damage repair mechanisms. This area is very complex, and I don’t think anyone fully understands it yet. It’s also difficult to study. I don't believe the rate of reverse transcription is the limiting factor here, although it could play a role for long or structured pegRNAs. You might have already come across this, but the PE6 generation of Prime Editors, which were released about half a year ago, involve engineered or evolved reverse transcriptases that are more processive and can more easily synthesize longer transcripts. Another factor that could play a role is the secondary structure of the guide RNA. Each prime editing guide RNA faces a common problem: it has a spacer that binds the bottom strand and a three-prime extension that binds the top strand. Since these two parts of the RNA bind complementary strands, they are also complementary to each other, meaning every prime editing guide has some tendency to bind itself. If the Gibbs free energy is too high, the guide RNA may fold in on itself, preventing it from binding to the prime editor, which then inhibits prime editing. Additionally, the three-prime extension itself can fold independently. I haven’t specifically examined this for the F508 delta guides, but it is something that can be predicted. There are tools available that can predict the secondary structure of an RNA sequence, and if there’s a significant hairpin structure, it might mean the three-prime extension remains closed, preventing the reverse transcriptase from using it as a template. The PE6 prime editors have been engineered to be more effective in such scenarios, being less affected by secondary structures and better able to read through them." />
- <QaBox q="What would be the application? Would you administer the heat shock in vivo, or...?" a="I believe they used it to engineer zebrafish embryos or something along those lines. It’s quite specific, of course. If you plan to deliver your guide RNA through a viral vector or similar method for human therapy, the application would differ significantly. You obviously can't administer a heat shock to humans, so it really depends on the context of your application." />
- <QaBox q="Given the time constraints, let's move on to the next question. Due to our limited resources, we are targeting a PE2 system, and we'd like to ask if you see any chances of success with this system. If so, how high do you think the chances of success are?" a="PE2 can work, but it really depends on your application and the methods you have to assess the editing efficiency. If you can use NGS (Next-Generation Sequencing) for everything, you'll be able to detect edits even with PE2 systems. However, I would generally expect the efficiency to be low. Whenever possible, I would always recommend trying the PE3 system. Could you share what your specific application is, or is that confidential?" />
- <QaBox q="So our goal is to eventually use it in vivo, but for now, we're focusing on trying to correct the mutation first in regular cell cultures and then later in primary cells." a="Is your focus specifically on the F508 delta mutation? If so, we could potentially help you get you started, as we already have constructs and cells with that mutation. We would need to discuss the financial aspects, but we might be able to assist. However, are you fully committed to targeting F508, or are you also considering other diseases or mutations?" />
- <QaBox q="The timeframe of the project, combined with the fact that we’re all studying on the side, limits us to a certain scope. Since this is our first time tackling a project like this, it makes sense to stick to something more manageable. So, we're somewhat committed to focusing on F508 due to these constraints." a="That's understandable. It can be really tough to juggle a project like this along with exams and studies, especially if you're also involved in competitions. But it's definitely worth the effort, even if you don't achieve huge results right away. The experience and learning, as well as the connections you make, are incredibly valuable. I'm a big supporter of such"/>
- <QaBox q="We have one patient who is willing to provide us with cells, but we don't have them yet." a="It sounds like you're aware of the challenges, and I don't want to discourage you, but just to be realistic, working with primary cells and getting everything ready could be tricky, especially considering the competition is in October. Experiments in human cells can take time, especially if you need to do multiple iterations or clone constructs—it could easily take a week or more per experiment." />
- <QaBox q="Regarding the cells we have, as mentioned in our paper, we screened all our guides on HEK cells with an integrated copy of the CFTR cDNA. HEK cells are easy to work with, but they don't naturally express CFTR, even though the gene is present in their genome. So, we introduced the mutation of interest into these cells, making it easier to screen." a="I'm not entirely sure if we can send over the cells due to ethical regulations, which can be complex and time-consuming to navigate. However, there's an alternative approach that might help you. Early on, we found that it's actually quite easy to screen guides using what we call a 'transient target.' In this method, you would transfect all your prime editing plasmids into HEK cells, along with a plasmid containing the CFTR cDNA with the mutation of interest." />
- <QaBox q="While this approach isn’t as physiological as editing the chromosome directly, our side-by-side comparisons showed almost equal efficiencies between transient and chromosomal targets. It's much easier and faster than working with patient-derived cells. I can definitely send you the plasmid, which would save you a lot of time and effort. This method is much simpler and could be a practical solution for your project." a="Our initial plan is to work with a reporter plasmid that expresses eGFP, where we've removed a splice site, until we have patient cells or cell lines with CFTR mutations. This will allow us to screen easily without needing to sequence everything. Do you maybe have any suggestions or advice on this approach?" />
- <QaBox q="Is that the PEAR system?" a="No, it’s a different one, but we also have a similar system. The advantage of this approach is that you can very easily see if it works, and it’s very sensitive—much easier than extracting and sequencing DNA. The downside, however, is that… actually, I’m not familiar with the 'flu PEAR system.'" />
- <QaBox q="Actually, we use the exact same system in our lab. It’s very useful for optimizing delivery strategies because it’s easy to see results. The downside, of course, is that the guides you’re using for that system aren’t specific to the F508 delta mutation, right? So, these are scientific trade-offs. You could, for example, design a reporter that uses your F508 delta guide and also results in fluorescence, but you would need to design the reporter first. It’s challenging to prove that it works because you might not have a perfect guide for F508 delta." a="It really depends on what you want to achieve. If your goal is to first check if you can successfully perform prime editing, then using the reporter is definitely a good first step." />
- <QaBox q="We will edit the plasmid, specifically the vector, so that we have almost the same pegRNA. The only difference will be downstream, behind the edit." a="Is this approach based on a paper from the Netherlands, or is it something you came up with yourself?" />
- <QaBox q="Based on a paper." a="Yeah, that sounds like a very good way to start. Do you already have the reporter plasmid ready?" />
- <QaBox q="Yeah, we bought the reporter, and now we’re making the necessary edits so we can use it." a="Okay, so do you also already have guides targeting F508 right now?" />
- <QaBox q="We’ve designed some guides, but we haven’t tested them yet. That’s one of our next steps. So, at the moment, we’re just in the design phase, or we have already designed them, and..." a="Yeah, okay, cool. Good luck with that! And I suppose you’re starting off with HEK cells as well, right?" />
- <QaBox q="We have HEK and HeLa cells, but we haven't decided yet which ones we'll use." a="I would start off in HEK cells because, by total accident or coincidence, they are much easier to achieve prime editing in. This is because the MLH1 gene, which negatively impacts prime editing outcomes, is naturally disabled in these cells—they don't produce the MLH1 protein. Of all cell lines available, HEK cells are the easiest to achieve editing with, so I would definitely recommend starting there." />
- <QaBox q="In terms of transfection, HEK cells are also very easily transfected. If I can offer another piece of advice, always include GFP controls—plasmids that simply express GFP without requiring editing—and use them to determine your transfection efficiency. It's crucial to have a very high transfection efficiency because you'll be working with a three-component system: your reporter, your prime editor, and your guides. All three plasmids need to be present in the same cell for the editing to occur, so you should aim for at least 70% transfection efficiency, preferably 80% or higher." a="I don't know what transfection method you're planning to use, but we've always used Lipofectamine 3000. It’s expensive, but it works very well. However, if you're looking for more cost-effective options, we recently discovered two other transfection reagents, Jet Optimus and Jet Prime, which are much cheaper and also work quite well. That said, I would advise against starting with any of the cheaper transfection reagents; you really need to aim for high transfection efficiency." />
- <QaBox q="Always make sure to measure and report transfection efficiency for every experiment because if it's low, the experiment might not yield useful results. If you have the funds or resources, I would also recommend designing P3 or even P3b guides, as they might offer better efficiency." a="When it comes to designing P3b guides, if you're primarily focused on P2 right now, there are some specific considerations to keep in mind. I'll provide you with a site that can help with this, and I'll give you the link in just a moment." />
- <QaBox q="So, it's very advisable to check the Doench score. Do you know what it is?" a="No, not really." />
- <QaBox q="There are papers by John Doench, an American researcher, from quite a while ago that, in my opinion, are some of the best around. He developed a comprehensive scoring matrix specifically for regular Cas9 that can evaluate the quality of the spacer in your guide RNA. This is important because Cas9 tends to prefer certain sequences over others. For instance, a good spacer should have an appropriate GC content and should avoid hairpins that might cause it to fold in on itself, which would prevent it from functioning properly. You can use this matrix to give a score for the quality of a guide RNA. I’m going to pull up an example here. The site from Synthego, a commercial provider of CRISPR reagents, allows you to check the quality of your guide. When you validate it, the site gives a score based on various factors, including off-target effects, although that might not be your primary concern at the moment. If you hover over a specific area, it will show you the Doench Score, which is crucial. Ideally, you want a guide with a good Doench Score. A good score starts at around 0.4, indicated by a green check mark for good efficiency. If the score is very low, it means that the guide likely has low CRISPR-Cas9 activity and may not be very efficient. When designing prime editing guides, RNA, we always check the spacer for a good Doench Score. If we are designing nicking guides for a PE3 or PE3b strategy, we also ensure that they have a good score. This is one of the easiest tools to check for that. Whenever possible, try using PE3. In some cases, PE3 performs better than PE2, though not always. PE3b might not always work either, but for many mutations, we have seen significant increases in editing efficiency by including the PE3 guide." a="Okay, yeah, that was quite clear from your results; the diagram illustrated that very well."/>
- <QaBox q="Are there more off-target effects when using PE3 since you have to make another cut?" a="If you decide to use PE3, it's important to be aware that while it's not exactly an off-target issue, there is a risk of an undesired on-target outcome. The concern with regular PE3 is that both strands of DNA can be nicked simultaneously, which can lead to a staggered double-strand break. This can result in the formation of indels (insertions or deletions). In your case, this means that if the region around the F508 delta mutation is broken, the prime editor might not be able to repair it properly, leading to additional base pairs being removed or added, and thus, the sequence might be altered in an unintended way. The risk of on-target indels is definitely higher with PE3 compared to PE2. However, this risk is reduced when using PE3b, which employs sequential nicking. The PE3b nicking guides are designed to recognize the wild-type sequence, and they can only nick the opposite strand if the correction has already been made on the top strand. This sequential action helps to avoid the generation of indels. Introducing a second guide into the system also brings the possibility of off-target editing by that guide however, since only a Cas9 nickase is used, off-target indels should be limited."/>
- <QaBox q="Yes, okay, thank you. Do you have time left, or are we out of time?" a="It's fine."/>
- <QaBox q="We have more or less one last question. If it’s not possible, that’s completely fine. We just wanted to ask if you could possibly forward the contact details for the Ussing chamber setup in Paris that you mentioned in your email. Would that be possible?" a="You can certainly try to contact them, but I actually know that there are quite good labs in Germany that work on similar things."/>
- <QaBox q="One major drawback for you might be the time it takes to differentiate cells. If you harvest stem cells or basal cells from patients, they will have the CFTR gene, but they don’t express it immediately. It takes about four weeks for them to differentiate and start producing the CFTR protein. Without this differentiation, you can't measure the currents, which could slow you down significantly. I'm not sure if you have that kind of time." a="If I can give you one piece of advice: it’s less physiological, but it’s still an accepted assay—try it on organoids. We could actually perform both assays here. If you find guides that work really well, we could consider doing those tests here. Someone could come over, or we could do the experiments if they’re not too expensive and have a good chance of working. I think we wouldn’t mind adding the F508 delta mutation to our list of editable mutations."/>
- <QaBox q="There’s also the possibility that if the paper from the Liu Lab is published within the next month, you could just use the guide they provide, and you’d have a guide that is known to work." a="Yeah, so I think if our guides don’t work as well as we hope, this could be an opportunity. We still want to explore optimization of the prime editing system, such as trying different reverse transcriptases or other methods. For now, we’d like to try it on our own, but like you said, it’s good to have this opportunity in case it doesn’t work out."/>
- <QaBox q="Yeah, I think working with patient cells is one thing, but just be aware that these models and assays typically take a lot of time—easily half a year, and that’s considered fast to get them up and running. Unless you're in a lab that already has experience with growing organoids, it could be very challenging to start from scratch." a="However, you can always try. The team in Paris that we know very well—they are incredibly kind, world-class experts in what they do, but they are also under a lot of pressure. They use these technologies not only for research but also to diagnose patients. What the French team has managed to do is show that if a patient’s cells respond to certain drugs, the government allows those drugs to be administered to the patient. You can imagine how important these experiments are, as they can directly impact patients' lives, which naturally takes the highest priority."/>
- <QaBox q="Yeah, we recognized that too. We talked with the CF team at the University Clinic in Münster and asked about using their Ussing chamber, but they are really overworked with it. That’s why we reached out to you about it. But it’s completely fine, as we mentioned before." a="I'm going to put it bluntly: Ussing chamber experiments, while they are highly regarded and provide valuable data, are a real pain to perform. They are incredibly time-consuming and have a very low throughput. A typical setup has four chambers, so you always need to do repeats. In the best-case scenario, you can test two conditions at a time. If you have a very experienced person, they might be able to run eight samples, but they would have to stay with the machine for four to five hours, maintaining constant attention. With multiple technicians, as is the case in France, you might manage to run 16 samples a day."/>
- <QaBox q="On top of that, the cells need to be differentiated properly, and you have to know how to handle them correctly. The medium required is very expensive, and working with these cells is almost more of an art than a science. You have to know when the cells look 'happy' or not because you don't want to waste time on cells that aren't in good condition. I've run quite a few of these assays myself, and while they are great for CF work and provide results that are relevant to patient outcomes, they are technically challenging and very demanding." a="If you want a functional output to show that the CFTR protein is working again, I would recommend starting with one of the easier models, like organoids. We also have in our lab 16HBE cells with a YFP sensor. I don't know if you've heard or read about that. These cells express YFP, which is sensitive to halide ions, including chloride and iodide. When you add a buffer containing these ions to the cells, the YFP intensity quenches. This is something we typically use in our experiments."/>
- <QaBox q="For wild-type cells, you see a rapid and dramatic quenching because CFTR allows these ions to enter the cells. In cells with the mutation, there’s no quenching because the channel isn’t working. While it’s less relevant because these aren't patient cells, it’s closer to reality. The 16HBE cell line is an airway epithelial line, and the expression of CFTR is endogenous, so it’s not at the exaggerated levels you might see in more artificial models like HEK cells." a="Using the YFP assay could be a good alternative or a Plan B for getting a functional readout. This assay is medium to high throughput—you can run entire 96-well plates in about half an hour. All you need for this is the cells and a plate reader that can measure fluorescence and inject the buffer. If you don’t have a plate reader with an injection system, you can also manually add the buffer and quickly place the plate in the machine."/>
- <QaBox q="Yes, that sounds quite good. I think we’ll definitely consider that as a method." a="If you have a little more time, I wanted to ask about the pegRNA. You stabilized it with a stem loop or some kind of motif in the paper, like the trevopreQ1. Did you test other motifs as well, or...?"/>
+ interview: <>
+ <QaBox q="You mentioned that it was quite challenging to target the F508del mutation. Could you provide more detailed reasons for why this is the case or explain why this mutation is particularly difficult to target compared to others?" a="Yes, that's the million-dollar question. First of all, let me clarify: our group has never directly worked on that mutation because we immediately focused on the drug-refractory mutations, such as nonsense mutations where the protein is not formed, indel mutations, or severe missense mutations that do not respond to modulator therapies. Of course, we know several groups in the field who either work on gene editing or focus on cystic fibrosis (CF). We've heard from some of them who attempted to target the F508del mutation. For example, some collaborators really tried to design different guides but were unable to find anything above the detection limit. F508del is probably one of the most logical mutations to try to correct, not just for CF but for the entire gene-editing field. If you look at the frequencies of mutations that cause genetic diseases, the F508del mutation is by far the most common deletion mutation causing a severe disease. This is because CF, along with sickle cell disease, is one of the most common deadly inherited diseases, and it's overrepresented within CF. So, it makes sense that they would have been trying to target it from the beginning. Interestingly, if you read the Prime Editing paper by Anzalone, F508del is mentioned in the introduction in connection with cystic fibrosis. So, it's somewhat surprising that after all this time—it's been almost five years now—they haven't published or released anything on F508del. However, last weekend, there was an online seminar where David Liu gave a talk, and he showed some unpublished data indicating that they managed to achieve quite good Prime Editing efficiency on F508del. It's worth noting that David Liu rarely presents unpublished data unless the publication is either accepted or very close to acceptance. So, we all kind of expect that the paper will be published soon, perhaps within the next week or at least within a month. From what I saw, it appears they leveraged many of the approaches available today to enhance Prime Editing. Now, regarding your question about why this mutation is so difficult to target with Prime Editing, I can't provide an exact answer. However, I can list some potential difficulties associated with the mutation, and it’s likely that F508del is challenging for several of these reasons. For instance, it could be related to the genomic region itself. Writing insertions can be more difficult; the easiest edits are single-point mutations, followed by deletions, and the most challenging are insertions. This difficulty arises because it involves writing a third strand and then relying on DNA damage repair mechanisms to fix it. It could also be that the region around the F508del mutation is challenging due to flap equilibration or that it attracts pathways such as mismatch repair that negatively impact Prime Editing. Additionally, the chromatin organization around that region could play a role. Over the past year, we’ve gathered clues that chromatin organization significantly affects Prime Editing capability, while this is much less of an issue for Cas9 and base editors. Studying this is not straightforward; you would need to conduct experiments like ATAC-seq to determine the chromatin organization around the mutation and how it might interfere. I also noticed on a slide that dsgRNAs were mentioned, though David Liu didn't discuss them in his talk. After looking them up online, I found that this technique, published a few years ago by other researchers, is specifically designed to open up chromatin. It seems they use different guides, without the three-prime extension, to open up the chromatin, which could be one way to overcome the limitations in Prime Editing efficiency. There could be other factors as well, and it’s often difficult to predict what will work and what won't. We have prediction tools for Prime Editing guides that work to some extent, but they are not as effective as the prediction tools available for regular CRISPR guide RNAs. This suggests that the Prime Editing system is more complex than the canonical CRISPR systems, with more variables that can influence success or failure. I hope this answers your question somewhat." />
+ <QaBox q="Perhaps we could quickly discuss which part of the prime editing complex you think plays the most significant role in making insertions much more challenging compared to deletions. Is it the reverse transcriptase or the RNA?" a="I don't think it's primarily the reverse transcriptase that's the issue. People have shown that longer insertions are definitely possible. I believe the challenge lies in the process when your cell has to repair the new DNA strand, which is generated and exists as a three-stranded intermediate. We don’t directly intervene in this process; it entirely depends on the cell and the DNA damage repair pathways active in those cells. Through expression of dominant negative DNA damage repair effectors, or by nicking the non-edited strand, the outcome can be steered to some extent. When you perform an insertion, the new strand must hybridize with the bottom strand, which remains intact. This creates a small loop that needs to be incorporated. At this point, the cell faces two options: it can either revert to the original state or incorporate the edit you’re trying to introduce. In certain circumstances, perhaps due to how the new DNA strand folds or the sequence context of the region of interest, the cell might heavily favor reverting to the original state, resulting in the absence of the intended edit. This process is extremely difficult to predict, but there are several indications pointing in this direction. For example, in the case of point mutations, it has been shown that it’s easier to convert a C to a G rather than the reverse, simply due to how these mismatches are recognized by the DNA damage repair mechanisms. This area is very complex, and I don’t think anyone fully understands it yet. It’s also difficult to study. I don't believe the rate of reverse transcription is the limiting factor here, although it could play a role for long or structured pegRNAs. You might have already come across this, but the PE6 generation of Prime Editors, which were released about half a year ago, involve engineered or evolved reverse transcriptases that are more processive and can more easily synthesize longer transcripts. Another factor that could play a role is the secondary structure of the guide RNA. Each prime editing guide RNA faces a common problem: it has a spacer that binds the bottom strand and a three-prime extension that binds the top strand. Since these two parts of the RNA bind complementary strands, they are also complementary to each other, meaning every prime editing guide has some tendency to bind itself. If the Gibbs free energy is too high, the guide RNA may fold in on itself, preventing it from binding to the prime editor, which then inhibits prime editing. Additionally, the three-prime extension itself can fold independently. I haven’t specifically examined this for the F508del guides, but it is something that can be predicted. There are tools available that can predict the secondary structure of an RNA sequence, and if there’s a significant hairpin structure, it might mean the three-prime extension remains closed, preventing the reverse transcriptase from using it as a template. The PE6 prime editors have been engineered to be more effective in such scenarios, being less affected by secondary structures and better able to read through them." />
+ <QaBox q="What would be the application? Would you administer the heat shock in vivo, or...?" a="I believe they used it to engineer zebrafish embryos or something along those lines. It’s quite specific, of course. If you plan to deliver your guide RNA through a viral vector or similar method for human therapy, the application would differ significantly. You obviously can't administer a heat shock to humans, so it really depends on the context of your application." />
+ <QaBox q="Given the time constraints, let's move on to the next question. Due to our limited resources, we are targeting a PE2 system, and we'd like to ask if you see any chances of success with this system. If so, how high do you think the chances of success are?" a="PE2 can work, but it really depends on your application and the methods you have to assess the editing efficiency. If you can use NGS (Next-Generation Sequencing) for everything, you'll be able to detect edits even with PE2 systems. However, I would generally expect the efficiency to be low. Whenever possible, I would always recommend trying the PE3 system. Could you share what your specific application is, or is that confidential?" />
+ <QaBox q="So our goal is to eventually use it in vivo, but for now, we're focusing on trying to correct the mutation first in regular cell cultures and then later in primary cells." a="Is your focus specifically on the F508del mutation? If so, we could potentially help you get you started, as we already have constructs and cells with that mutation. We would need to discuss the financial aspects, but we might be able to assist. However, are you fully committed to targeting F508, or are you also considering other diseases or mutations?" />
+ <QaBox q="The timeframe of the project, combined with the fact that we’re all studying on the side, limits us to a certain scope. Since this is our first time tackling a project like this, it makes sense to stick to something more manageable. So, we're somewhat committed to focusing on F508 due to these constraints." a="That's understandable. It can be really tough to juggle a project like this along with exams and studies, especially if you're also involved in competitions. But it's definitely worth the effort, even if you don't achieve huge results right away. The experience and learning, as well as the connections you make, are incredibly valuable. I'm a big supporter of such" />
+ <QaBox q="We have one patient who is willing to provide us with cells, but we don't have them yet." a="It sounds like you're aware of the challenges, and I don't want to discourage you, but just to be realistic, working with primary cells and getting everything ready could be tricky, especially considering the competition is in October. Experiments in human cells can take time, especially if you need to do multiple iterations or clone constructs—it could easily take a week or more per experiment." />
+ <QaBox q="Regarding the cells we have, as mentioned in our paper, we screened all our guides on HEK cells with an integrated copy of the CFTR cDNA. HEK cells are easy to work with, but they don't naturally express CFTR, even though the gene is present in their genome. So, we introduced the mutation of interest into these cells, making it easier to screen." a="I'm not entirely sure if we can send over the cells due to ethical regulations, which can be complex and time-consuming to navigate. However, there's an alternative approach that might help you. Early on, we found that it's actually quite easy to screen guides using what we call a 'transient target.' In this method, you would transfect all your prime editing plasmids into HEK cells, along with a plasmid containing the CFTR cDNA with the mutation of interest." />
+ <QaBox q="While this approach isn’t as physiological as editing the chromosome directly, our side-by-side comparisons showed almost equal efficiencies between transient and chromosomal targets. It's much easier and faster than working with patient-derived cells. I can definitely send you the plasmid, which would save you a lot of time and effort. This method is much simpler and could be a practical solution for your project." a="Our initial plan is to work with a reporter plasmid that expresses eGFP, where we've removed a splice site, until we have patient cells or cell lines with CFTR mutations. This will allow us to screen easily without needing to sequence everything. Do you maybe have any suggestions or advice on this approach?" />
+ <QaBox q="Is that the PEAR system?" a="No, it’s a different one, but we also have a similar system. The advantage of this approach is that you can very easily see if it works, and it’s very sensitive—much easier than extracting and sequencing DNA. The downside, however, is that… actually, I’m not familiar with the 'flu PEAR system.'" />
+ <QaBox q="Actually, we use the exact same system in our lab. It’s very useful for optimizing delivery strategies because it’s easy to see results. The downside, of course, is that the guides you’re using for that system aren’t specific to the F508del mutation, right? So, these are scientific trade-offs. You could, for example, design a reporter that uses your F508del guide and also results in fluorescence, but you would need to design the reporter first. It’s challenging to prove that it works because you might not have a perfect guide for F508del." a="It really depends on what you want to achieve. If your goal is to first check if you can successfully perform prime editing, then using the reporter is definitely a good first step." />
+ <QaBox q="We will edit the plasmid, specifically the vector, so that we have almost the same pegRNA. The only difference will be downstream, behind the edit." a="Is this approach based on a paper from the Netherlands, or is it something you came up with yourself?" />
+ <QaBox q="Based on a paper." a="Yeah, that sounds like a very good way to start. Do you already have the reporter plasmid ready?" />
+ <QaBox q="Yeah, we bought the reporter, and now we’re making the necessary edits so we can use it." a="Okay, so do you also already have guides targeting F508 right now?" />
+ <QaBox q="We’ve designed some guides, but we haven’t tested them yet. That’s one of our next steps. So, at the moment, we’re just in the design phase, or we have already designed them, and..." a="Yeah, okay, cool. Good luck with that! And I suppose you’re starting off with HEK cells as well, right?" />
+ <QaBox q="We have HEK and HeLa cells, but we haven't decided yet which ones we'll use." a="I would start off in HEK cells because, by total accident or coincidence, they are much easier to achieve prime editing in. This is because the MLH1 gene, which negatively impacts prime editing outcomes, is naturally disabled in these cells—they don't produce the MLH1 protein. Of all cell lines available, HEK cells are the easiest to achieve editing with, so I would definitely recommend starting there." />
+ <QaBox q="In terms of transfection, HEK cells are also very easily transfected. If I can offer another piece of advice, always include GFP controls—plasmids that simply express GFP without requiring editing—and use them to determine your transfection efficiency. It's crucial to have a very high transfection efficiency because you'll be working with a three-component system: your reporter, your prime editor, and your guides. All three plasmids need to be present in the same cell for the editing to occur, so you should aim for at least 70% transfection efficiency, preferably 80% or higher." a="I don't know what transfection method you're planning to use, but we've always used Lipofectamine 3000. It’s expensive, but it works very well. However, if you're looking for more cost-effective options, we recently discovered two other transfection reagents, Jet Optimus and Jet Prime, which are much cheaper and also work quite well. That said, I would advise against starting with any of the cheaper transfection reagents; you really need to aim for high transfection efficiency." />
+ <QaBox q="Always make sure to measure and report transfection efficiency for every experiment because if it's low, the experiment might not yield useful results. If you have the funds or resources, I would also recommend designing P3 or even P3b guides, as they might offer better efficiency." a="When it comes to designing P3b guides, if you're primarily focused on P2 right now, there are some specific considerations to keep in mind. I'll provide you with a site that can help with this, and I'll give you the link in just a moment." />
+ <QaBox q="So, it's very advisable to check the Doench score. Do you know what it is?" a="No, not really." />
+ <QaBox q="There are papers by John Doench, an American researcher, from quite a while ago that, in my opinion, are some of the best around. He developed a comprehensive scoring matrix specifically for regular Cas9 that can evaluate the quality of the spacer in your guide RNA. This is important because Cas9 tends to prefer certain sequences over others. For instance, a good spacer should have an appropriate GC content and should avoid hairpins that might cause it to fold in on itself, which would prevent it from functioning properly. You can use this matrix to give a score for the quality of a guide RNA. I’m going to pull up an example here. The site from Synthego, a commercial provider of CRISPR reagents, allows you to check the quality of your guide. When you validate it, the site gives a score based on various factors, including off-target effects, although that might not be your primary concern at the moment. If you hover over a specific area, it will show you the Doench Score, which is crucial. Ideally, you want a guide with a good Doench Score. A good score starts at around 0.4, indicated by a green check mark for good efficiency. If the score is very low, it means that the guide likely has low CRISPR-Cas9 activity and may not be very efficient. When designing prime editing guides, RNA, we always check the spacer for a good Doench Score. If we are designing nicking guides for a PE3 or PE3b strategy, we also ensure that they have a good score. This is one of the easiest tools to check for that. Whenever possible, try using PE3. In some cases, PE3 performs better than PE2, though not always. PE3b might not always work either, but for many mutations, we have seen significant increases in editing efficiency by including the PE3 guide." a="Okay, yeah, that was quite clear from your results; the diagram illustrated that very well." />
+ <QaBox q="Are there more off-target effects when using PE3 since you have to make another cut?" a="If you decide to use PE3, it's important to be aware that while it's not exactly an off-target issue, there is a risk of an undesired on-target outcome. The concern with regular PE3 is that both strands of DNA can be nicked simultaneously, which can lead to a staggered double-strand break. This can result in the formation of indels (insertions or deletions). In your case, this means that if the region around the F508del mutation is broken, the prime editor might not be able to repair it properly, leading to additional base pairs being removed or added, and thus, the sequence might be altered in an unintended way. The risk of on-target indels is definitely higher with PE3 compared to PE2. However, this risk is reduced when using PE3b, which employs sequential nicking. The PE3b nicking guides are designed to recognize the wild-type sequence, and they can only nick the opposite strand if the correction has already been made on the top strand. This sequential action helps to avoid the generation of indels. Introducing a second guide into the system also brings the possibility of off-target editing by that guide however, since only a Cas9 nickase is used, off-target indels should be limited." />
+ <QaBox q="Yes, okay, thank you. Do you have time left, or are we out of time?" a="It's fine." />
+ <QaBox q="We have more or less one last question. If it’s not possible, that’s completely fine. We just wanted to ask if you could possibly forward the contact details for the Ussing chamber setup in Paris that you mentioned in your email. Would that be possible?" a="You can certainly try to contact them, but I actually know that there are quite good labs in Germany that work on similar things." />
+ <QaBox q="One major drawback for you might be the time it takes to differentiate cells. If you harvest stem cells or basal cells from patients, they will have the CFTR gene, but they don’t express it immediately. It takes about four weeks for them to differentiate and start producing the CFTR protein. Without this differentiation, you can't measure the currents, which could slow you down significantly. I'm not sure if you have that kind of time." a="If I can give you one piece of advice: it’s less physiological, but it’s still an accepted assay—try it on organoids. We could actually perform both assays here. If you find guides that work really well, we could consider doing those tests here. Someone could come over, or we could do the experiments if they’re not too expensive and have a good chance of working. I think we wouldn’t mind adding the F508del mutation to our list of editable mutations." />
+ <QaBox q="There’s also the possibility that if the paper from the Liu Lab is published within the next month, you could just use the guide they provide, and you’d have a guide that is known to work." a="Yeah, so I think if our guides don’t work as well as we hope, this could be an opportunity. We still want to explore optimization of the prime editing system, such as trying different reverse transcriptases or other methods. For now, we’d like to try it on our own, but like you said, it’s good to have this opportunity in case it doesn’t work out." />
+ <QaBox q="Yeah, I think working with patient cells is one thing, but just be aware that these models and assays typically take a lot of time—easily half a year, and that’s considered fast to get them up and running. Unless you're in a lab that already has experience with growing organoids, it could be very challenging to start from scratch." a="However, you can always try. The team in Paris that we know very well—they are incredibly kind, world-class experts in what they do, but they are also under a lot of pressure. They use these technologies not only for research but also to diagnose patients. What the French team has managed to do is show that if a patient’s cells respond to certain drugs, the government allows those drugs to be administered to the patient. You can imagine how important these experiments are, as they can directly impact patients' lives, which naturally takes the highest priority." />
+ <QaBox q="Yeah, we recognized that too. We talked with the CF team at the University Clinic in Münster and asked about using their Ussing chamber, but they are really overworked with it. That’s why we reached out to you about it. But it’s completely fine, as we mentioned before." a="I'm going to put it bluntly: Ussing chamber experiments, while they are highly regarded and provide valuable data, are a real pain to perform. They are incredibly time-consuming and have a very low throughput. A typical setup has four chambers, so you always need to do repeats. In the best-case scenario, you can test two conditions at a time. If you have a very experienced person, they might be able to run eight samples, but they would have to stay with the machine for four to five hours, maintaining constant attention. With multiple technicians, as is the case in France, you might manage to run 16 samples a day." />
+ <QaBox q="On top of that, the cells need to be differentiated properly, and you have to know how to handle them correctly. The medium required is very expensive, and working with these cells is almost more of an art than a science. You have to know when the cells look 'happy' or not because you don't want to waste time on cells that aren't in good condition. I've run quite a few of these assays myself, and while they are great for CF work and provide results that are relevant to patient outcomes, they are technically challenging and very demanding." a="If you want a functional output to show that the CFTR protein is working again, I would recommend starting with one of the easier models, like organoids. We also have in our lab 16HBE cells with a YFP sensor. I don't know if you've heard or read about that. These cells express YFP, which is sensitive to halide ions, including chloride and iodide. When you add a buffer containing these ions to the cells, the YFP intensity quenches. This is something we typically use in our experiments." />
+ <QaBox q="For wild-type cells, you see a rapid and dramatic quenching because CFTR allows these ions to enter the cells. In cells with the mutation, there’s no quenching because the channel isn’t working. While it’s less relevant because these aren't patient cells, it’s closer to reality. The 16HBE cell line is an airway epithelial line, and the expression of CFTR is endogenous, so it’s not at the exaggerated levels you might see in more artificial models like HEK cells." a="Using the YFP assay could be a good alternative or a Plan B for getting a functional readout. This assay is medium to high throughput—you can run entire 96-well plates in about half an hour. All you need for this is the cells and a plate reader that can measure fluorescence and inject the buffer. If you don’t have a plate reader with an injection system, you can also manually add the buffer and quickly place the plate in the machine." />
+ <QaBox q="Yes, that sounds quite good. I think we’ll definitely consider that as a method." a="If you have a little more time, I wanted to ask about the pegRNA. You stabilized it with a stem loop or some kind of motif in the paper, like the trevopreQ1. Did you test other motifs as well, or...?" />
</>,
references: [<ol>{/*<!-- Citation num 1--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-1">
@@ -498,28 +530,72 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>).
<a className="doi" href="https://doi.org/10.1016/j.xcrm.2024.101544"> doi: 10.1016/j.xcrm.2024.101544</a>
</li>
-
- </ol>]
+
+ </ol>],
+ summary: ""
},
- {
+ {
vorname: "Nicole",
- nachnname: "Friedlein",
+ nachnname: "Friedlein",
job: "Research group on fundamental rights",
affiliation: "Universität Potsdam",
- pictureurl: pics['placeholder'],
+ pictureurl: pics['nicole'],
tag: "Academia",
heading: "Discussion on how health insurance companies manage cystic fibrosis patients and gene therapy treatments",
interviewtabid: "nicole",
cardtext: "",
language: "de",
- quote: "",
+ quote: "Public health insurance operates under an economic efficiency principle, meaning the most cost-effective treatments are preferred. But if gene therapies become the only treatment option for certain conditions, they will likely have to be included in the coverage, which could be a challenge for the system.",
aimofcontact: "The main objective of the contact was to learn from the discussion on issues related to cystic fibrosis (CF), gene therapy, health insurance processes and regulatory pathways. In particular, we wanted to understand the real-world challenges and technical aspects of gene editing, especially prime editing, as well as the complexities of approval and reimbursement of gene therapies for CF patients.",
insights: "The regulatory approval process, particularly by the European Medicines Agency (EMA) for advanced medical devices, has highlighted the bureaucratic hurdles that gene therapies must overcome. We learned that such therapies for cystic fibrosis have to navigate complex European and German regulatory systems. The discussion on the AMNOG process was crucial. We learnt that the additional benefit of a therapy is assessed for reimbursement by the statutory health insurance funds. We implemented this insight in our project by considering the long-term regulatory and economic effects as important milestones for therapy development. We also gained insight into how public and private health insurers may differ in their reimbursement of such therapies. Public insurers have stricter guidelines, while private insurers can be more flexible, but both require strict justification, especially for rare diseases such as cystic fibrosis. Information on newborn screening and genetic counselling covered by public health insurance was crucial to understanding how preventive measures for CF are managed. This underlines the importance of early intervention and diagnosis in our project. Atypical forms of CF, where health insurance companies do not cover treatment due to non-standardised test results, were identified as a key problem. This helped us to recognise the need for more adaptable insurance policies and clearer pathways for the treatment of atypical cases in our project plans. The debate about whether healthcare systems can afford the high costs of gene therapies highlighted an important issue in the current medical landscape. We have incorporated this insight into our project by discussing possible cost-effective alternatives and the need for thorough cost-benefit analysis in the development of treatments.",
implementation: "After the interview, we further tailored our project to focus on a simple delivery method. To gain an overview of the regulatory requirements and to better deliver the project, one of our team members attended a GxP course to ensure we met all the necessary standards. To deepen our knowledge of entrepreneurship, we conducted further interviews with start-ups and industrial companies, which gave us important insights into practical implementation. These steps ensure that our project is not only based on scientific research, but also takes into account the practical, regulatory and social aspects that are crucial to bringing new CF therapies to the market. We are currently developing strategies to successfully implement our ideas and the project in the future.",
+ interview: <>
+ <QaBox q="To start with this interview. Do you have any questions about this project?"
+ a="Are you writing a paper on this, or are you conducting actual laboratory research? Or is it primarily literature review? How does your work look?" />
+ <QaBox q="It’s not just literature review, though we do start with that. We have a lot of lab work ahead of us. Ideally, we would have a finished construct to present at the end, maybe even a functional gene therapy, though that’s quite ambitious and probably not possible in the short time frame. We’re working on various gene-editing approaches and testing plasmids in HEK cells. We are also exploring Prime Editing and trying to improve its efficiency using different reverse transcriptase enzymes. So, it’s a mix of lab work, literature research, and preparing for a presentation at a competition."
+ a="Are you writing a formal paper?" />
+ <QaBox q="We’re not writing a formal text-based paper, but everything will be available on a website. We will document most of our work on the website, with sub-pages detailing lab work, interviews, and research."
+ a="What exactly is Prime Editing, and how does it differ from altering the germline? Where in the genome does this therapy act?" />
+ <QaBox q="Our current plan is to deliver the therapy via a lipid nanoparticle system, which will be inhaled and go into the lungs. While cystic fibrosis (CF) affects all mucus membranes, the lungs are the most critical area, so we’re focusing on that. The therapy will only target surface cells in the lungs, not the basal cells responsible for producing new lung cells."
+ a="Thank you for giving me insights into your project." />
+ <QaBox q="Do you know how cystic fibrosis (CF) approval works in terms of health insurance and regulatory processes?"
+ a="The approval process for gene therapies is primarily done through the EMA (European Medicines Agency) under specific EU regulations for Advanced Medical Products, including gene therapies. There is also a national approval process in Germany for individualized treatments, but large-scale therapies must go through the EU process." />
+ <QaBox q="Can you share more about the approval and reimbursement processes for CF treatment?"
+ a="The approval process is separate from reimbursement by public health insurance. CF is considered a rare disease if it affects fewer than five out of 10,000 people, and treatments for rare diseases often face special reimbursement challenges. If more than five out of 10,000 people are affected, the disease is relatively common, and approval and reimbursement go through a different procedure known as the AMNOG process. For more common diseases, an additional benefit (Zusatznutzen) must be demonstrated during the approval process." />
+ <QaBox q="Have you heard about issues with reimbursement from private insurance companies?"
+ a="We’ve heard that private insurance companies can make it difficult to get treatments reimbursed, especially experimental ones. One of our colleagues almost had to go to court to get his treatment reimbursed by his private insurer, which was quite expensive. Eventually, he switched to public insurance, but the situation was difficult." />
+ <QaBox q="Why did your colleague have issues with private insurance?"
+ a="He was privately insured, but the treatment was very expensive, around €16,000 per month, and the insurance company was reluctant to cover it." />
+ <QaBox q="Do you need legal information for your project?"
+ a="Both. We want to be well-informed to identify potential obstacles early on, such as legal restrictions or bans on altering certain chromosomes. Although we won’t be running clinical trials, understanding the regulatory landscape is crucial for our future planning." />
+ <QaBox q="How does genetic counseling and testing work for CF?"
+ a="Genetic counseling and testing are usually covered by health insurance if there’s a medical reason, such as a family history or suspicion that the parents might be carriers. However, if both parents are healthy and there’s no family history of CF, insurance might not cover the tests." />
+ <QaBox q="Are there differences between public and private insurers for genetic tests?"
+ a="Public insurance has different regulations than private insurance, but I’m not entirely sure if that leads to different decisions regarding genetic testing. I can look into the public insurance regulations if that would be helpful." />
+ <QaBox q="Is newborn screening for CF covered by health insurance?"
+ a="Yes, newborn screening is part of a set of health examinations for children and adolescents, regulated under §26 SGB V (Social Security Code). Since it’s part of the regular screening process, it’s covered by health insurance without additional requirements." />
+ <QaBox q="How does public insurance handle CF treatment when a test comes back negative?"
+ a="Public health insurance works with standardized guidelines, and if a test comes back negative, it may no longer meet the criteria for coverage. However, if a doctor reconfirms the diagnosis, the treatment should continue to be covered." />
+ <QaBox q="Is there no rule that says genetic diseases, once diagnosed, should remain covered since genetics don’t change?"
+ a="In theory, yes. But the guidelines are usually based on medical evidence at the time, and re-testing can sometimes lead to complications in terms of coverage if the result differs. However, with proper medical documentation, it should be possible to maintain coverage." />
+ <QaBox q="Have recent changes in gene therapy costs impacted public health insurance?"
+ a="Not much has changed. It’s a political and societal question—how willing are we to finance these expensive therapies? Right now, public health insurance operates under an economic efficiency principle, meaning the most cost-effective treatments are preferred. But if gene therapies become the only treatment option for certain conditions, they will likely have to be included in the coverage, and it could be a challenge for the system. There are also ongoing price negotiations between insurers and manufacturers." />
+ <QaBox q="Do patents play a significant role in keeping gene therapy costs high?"
+ a="Yes, patents certainly influence the price, but the production of gene therapies is inherently expensive due to the complex research and manufacturing process." />
+ <QaBox q="Would private supplemental insurance be an option for covering expensive gene therapies?"
+ a="It’s possible that private supplemental insurance could cover these therapies if public health insurance doesn’t. However, this raises concerns about equity and accessibility. If public insurance doesn’t cover it, the burden might fall on private insurance, which could create disparities in access to treatment." />
+ <QaBox q="Is gene therapy research driven more by biology or medicine?"
+ a="It’s definitely interdisciplinary. Both biologists and medical professionals contribute. For example, at our university, the medical and biology faculties collaborate closely. Biologists usually handle the research, while medical professionals focus more on clinical applications." />
+ <QaBox q="Do biologists or medical professionals develop gene therapies?"
+ a="In terms of development, it’s mainly biologists and biotechnologists. Medical professionals get involved primarily in clinical trials. Some doctors do research, but they’re often needed in hospitals, so hands-on development is mostly handled by molecular biologists or biotechnologists." />
+ <QaBox q="Does research in genome medicine and gene therapies come from biology, medicine, or both?"
+ a="It’s mainly interdisciplinary. A lot of funding comes from industry, like BioNTech, or foundations like Mukoviszidose e.V., which funds research on cystic fibrosis. But in terms of practical research, it’s usually biologists or biotechnologists. Without industry support, research can struggle due to a lack of funding, so having backing is essential." />
+ </>,
+ summary: ""
},
- {
+ {
vorname: "Katrin",
- nachnname: "Westhoff",
+ nachnname: "Westhoff",
job: "physiotherapist",
affiliation: "Independent",
pictureurl: pics['westhoff'],
@@ -533,28 +609,28 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
insights: "During the sessions, we could ask Katrin as well as the respective parents and children questions. We learned that breathing therapy is also useful for other illnesses and that you can easily do some of the exercises yourself. Despite having cystic fibrosis, the children were better at the breathing exercises than we and Katrin were! The sessions take 30 to 60 minutes and include both manual therapy and playful elements to help engage the children. Most older children range from mildly unhappy to enthusiastic, but babies often cry during the treatments as it feels uncomfortable. This is often hard on the parents even though the treatment brings good results. A lot of children tend to hide that they have mucus sitting in their lungs by suppressing coughs. Especially with young children, it is important to stay on top of it and do regular breathing therapy even if it seems like it is currently not necessary. We also learned about the various informational material aimed at children to help explain therapies and symptoms to them and what accessories for breathing therapy there are. For example, a flutter is to train breathing out forcefully by breathing against a small weight and a binder can be worn at night to promote deep breathing. ",
implementation: "The most important thing was that both Katrin and the parents agreed that the children were able to inhale at an early age and that there were generally no physical problems with inhalation in general. This reinforced our decision to work towards delivery by inhalation. It was very interesting to see the different ways children deal with their exercises and hear about the progress they made. ",
text: [<ol>
- <li>
+ <li>
<strong>Robin (>10)</strong>
<p>Robin will soon start 4th grade and takes modulators. Since taking them, many problems have subsided. No regular pneumonia with long hospital stays and the mucus comes out easier. Nevertheless, Robin still goes to physiotherapy regularly to do manual breathing therapy to get the mucus out. Katrin tells us how the mucus changes color the longer it stays in the lungs. The new mucus is white, and the older mucus gets yellow first and then gets darker with time until it reaches a black color. Nowadays, Robin rarely has dark mucus or clumps, but we can still hear the rustling as Katrin starts the autogenous drainage (Autogene Drainage) by pressing on Robin's chest. The goal is to get out the mucus deep in the lungs. To do that, Robin must repeat the routine – breathing in deeply, holding, breathing out – multiple times and then cough and spit the mucus out. Sometimes it works, but other times the mucus does not come out easily. While according to Katrin the autogenous drainage is the gold standard, they do other useful exercises, too. For example, pressing the Vojta points (which the children call “the magic pointsâ€) on the chest to activate a deep breathing reflex and get air into parts of the lungs that may not have been used previously. Or physical activity such as climbing a few steps on a climbing ladder and hanging on it to stretch the thorax muscles.</p>
- </li>
- <li>
+ </li>
+ <li>
<strong>Sam (<10) & Alex (<10)</strong>
<p>Sam and Alex are siblings and do not have CF but another affliction that causes a persistent cough. They come together with a parent twice a week and do hanging exercises from the ceiling, nasal showers with needleless syringes, and the “magic points.†Katrin also checks their lungs for mucus in a similar manner to autogenous drainage. We, too, tried to do the nasal shower, and being a grown-up really does not guarantee being able to do that properly! This highlighted that the children know all their exercises by heart at a young age. On request, their parent told us that the physiotherapy made a big difference for both of them.</p>
- </li>
- <li>
+ </li>
+ <li>
<strong>Toni (<5)</strong>
<p>Toni has a light version of CF and has been doing physiotherapy with Katrin since shortly after birth. In contrast to most children we met or talked about, Toni refuses medication. Modulators are a possibility, but them and 'everything stinky' is a no-go, even though inhaling would be very beneficial due to the mucus buildup. Most exercises result in crying and screaming, which is very exhausting for the child. Due to the light nature of Toni's variant, they are not in danger, but a permanent therapy would be very beneficial.</p>
- </li>
- <li>
+ </li>
+ <li>
<strong>Chrissi (>10)</strong>
<p>Chrissi takes modulators and will soon take a trip to a water park with some friends. Katrin teaches us that when the children do not breathe out properly, air stays in the lungs and causes hyperinflation – with which it is actually harder to float in water! After the manual drainage, Katrin gets all of us glasses with water and dish soap and straws. Blowing bubbles is a playful way to train how to properly breathe out by either trying to blow bubbles as long as possible or trying to make an existing bubble as big as possible!</p>
- </li>
- </ol>,]
-
+ </li>
+ </ol>,],
+ summary: ""
},
- {
+ {
vorname: "Julia",
- nachnname: "XXX",
+ nachnname: "XXX",
job: "parent",
affiliation: "independent",
pictureurl: pics['julia'],
@@ -564,79 +640,80 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
language: "de",
quote: "At first, our world fell apart. I still remember the conversation with the doctor. ",
- aimofcontact: [ <p>We learned from our discussion with Max [Link Max] that cystic fibrosis (CF) has a profound impact on the whole family – not just the patient. In order to gain further insight into this subject, we sought to engage with the next of kin of CF patients.
- We were able to make contact with Julia through the self-help group of Mukviszidose e.V. [Link https://www.muko.info/ ], of which Max is a member. She subsequently reached out to us following Max's request for potential candidates for an interview with a patient group.
+ aimofcontact: [<p>We learned from our discussion with Max [Link Max] that cystic fibrosis (CF) has a profound impact on the whole family – not just the patient. In order to gain further insight into this subject, we sought to engage with the next of kin of CF patients.
+ We were able to make contact with Julia through the self-help group of Mukviszidose e.V. [Link https://www.muko.info/ ], of which Max is a member. She subsequently reached out to us following Max's request for potential candidates for an interview with a patient group.
She and her husband have a six-year-old daughter carrying the F508del mutation in the CFTR gene and a toddler without CF. </p>],
- insights: [<p> The interview with Julia shifted our focus to a new group of stakeholders: The patient’s support systems. Most people do not get genetically tested before having children and due to that, many people could get in the position of having a loved one with CF.
- We considered the societal impacts, such as the rising health care costs, which Nicole Friedlein emphasized during our interview. She explained how the long-term nature of treatment, frequent hospital visits, and the need for specialized medications place a significant
- financial burden on both patients and the health care system. This insight shaped our understanding of the broader economic challenges faced by families and institutions involved in managing chronic illnesses. Meanwhile, Julia brought attention to the psychological impact,
+ insights: [<p> The interview with Julia shifted our focus to a new group of stakeholders: The patient’s support systems. Most people do not get genetically tested before having children and due to that, many people could get in the position of having a loved one with CF.
+ We considered the societal impacts, such as the rising health care costs, which Nicole Friedlein emphasized during our interview. She explained how the long-term nature of treatment, frequent hospital visits, and the need for specialized medications place a significant
+ financial burden on both patients and the health care system. This insight shaped our understanding of the broader economic challenges faced by families and institutions involved in managing chronic illnesses. Meanwhile, Julia brought attention to the psychological impact,
stressing the emotional strain that accompanies not only the illness itself but also the financial pressures. She also showed us more perspectives on parenting of children with CF, than we heard before, and told us about the way from the first diagnosis to growing accustomed
to and living with a child with CF. Julia also confirmed that most children will have no issue using an inhalative therapy like we envision our gene therapy to be and shone light onto the comparatively very good situation for CF patients in Germany. </p>],
- implementation: [<p> This interview helped us confirm the delivery method we planned to use as we were previously concerned how and if children would be able to use the inhalative therapy. Besides that, Julia gave us further insights into the emotional side of
+ implementation: [<p> This interview helped us confirm the delivery method we planned to use as we were previously concerned how and if children would be able to use the inhalative therapy. Besides that, Julia gave us further insights into the emotional side of
dealing with CF and we were able to discuss the situation for patients in Germany in comparison to other countries better in later interviews [Link Joshua]. </p>],
interview: <>
- <QaBox q="Can you tell us a bit about your family? How old are your children and yourselves?" a="I’m 37, my husband is 44, and our daughter is six, turning seven soon. We also have a son who’s about a year and a half." />
- <QaBox q="Does your son also have cystic fibrosis?" a="No, he doesn’t." />
- <QaBox q="When was your daughter diagnosed with cystic fibrosis?" a="Right after birth. She was transferred to a bigger hospital due to an intestinal blockage and had surgery. After about two to three weeks in intensive care, the cystic fibrosis diagnosis came through newborn screening. At that time, the results took longer to process than they do now." />
- <QaBox q="That intestinal issue can happen for many reasons, right?" a="Yes, it was all new to us. The beginning was difficult, but things have gotten better since then, and we’re very grateful." />
- <QaBox q="How did you feel when you first heard the diagnosis?" a="It felt like our world was falling apart. I still remember the moment—it was like being in a movie. We were told in a separate room, and it felt overwhelming. One doctor even suggested we go home to think about it in peace, but all I could think about was returning to my child. It was a lot to take in, especially thinking about how we’d tell our family." />
- <QaBox q="That sounds incredibly hard. How did you handle it as time passed?" a="It was tough, but we were fortunate to have a doctor who really understood what we were going through, as he had a disabled child himself. He never scared us unnecessarily and guided us step by step, which made a big difference. We know many families who live in constant fear, but since those first months, we’ve learned to manage the situation without being overwhelmed by fear." />
- <QaBox q="Did any particular support help your family adjust to the diagnosis?" a="Yes, the rehab program we attended was a huge help. It was a family-oriented program, so my husband could be there too, which was important since I manage most things day-to-day. It really helped our daughter realize she’s not alone—she met other kids with similar conditions, which was a huge comfort." />
- <QaBox q="How did you explain the illness to your daughter?" a="We try to give it as little attention as possible in daily life. She’s been inhaling medication since she was eight weeks old, and it’s just part of her routine now. Thankfully, she doesn’t fight it or question it much, and her school and kindergarten haven’t made a big deal of it either, which is what we wanted." />
- <QaBox q="Does she ever ask about her illness compared to her younger brother, who doesn’t have cystic fibrosis?" a="She does sometimes ask why she’s sick and he’s not, but she’s not upset by it. We’ve made sure not to give her any special treatment because of her illness, which can be hard at times, but we want her to understand that her illness doesn’t define her." />
- <QaBox q="That sounds like a good balance. What about medications—did she start on any special treatments?" a="Yes, she started on Orkambi at around three years old but had to stop briefly due to high liver values. Now she’s on Kaftrio, which she started shortly before her sixth birthday, and it’s been going well." />
- <QaBox q="Did you face any issues with the health insurance for covering these medications?" a="Fortunately, no. We have statutory health insurance, and they’ve covered everything without any issues. We’ve heard it can be more complicated for those with private insurance." />
- <QaBox q="Have you ever had difficulties with access to medication?" a="Yes, there have been times when we’ve had to wait a few days for certain medications, like Kreon or antibiotics, especially in the winter. But we always plan ahead and keep a buffer, so we’ve never been without what we need." />
- <QaBox q="What would you say has been the most affected area for your daughter?" a="Her intestines are the most affected. Before she started Kaftrio, she had fatty stools and frequent bowel movements, even with the right Kreon dosage. Since starting Kaftrio, this has improved significantly." />
- <QaBox q="What kind of support would you have liked to receive earlier?" a="We wish we had been given more information about available services early on. We found out about Mukoviszidose e.V. from another family, not from our doctor. It would have been helpful to know about these resources right from the start." />
- <QaBox q="How about psychosocial support?" a="Initially, we didn’t have any psychological support—our doctor took care of everything. Now, where we live, there are more resources, and we think it’s a good thing. The rehab helped a lot in coming to terms with everything. We wish we had known about such services sooner." />
- <QaBox q="Does your daughter do physiotherapy?" a="Yes, once a week for about an hour. She’s been going since she was discharged from the hospital, and she has a close bond with her physiotherapist. They’ve been working together since she was a baby, and she goes by herself now." />
- <QaBox q="Are there any restrictions for her in terms of physical activities?" a="No, not really. She does dancing once a week, physiotherapy, and she’s even done a swimming course without any problems." />
- <QaBox q="How do you handle communicating about her illness?" a="We try not to make a big deal of it. When I looked for information, I found what we needed. There’s nothing we’ve really felt was missing." />
- </>
+ <QaBox q="Can you tell us a bit about your family? How old are your children and yourselves?" a="I’m 37, my husband is 44, and our daughter is six, turning seven soon. We also have a son who’s about a year and a half." />
+ <QaBox q="Does your son also have cystic fibrosis?" a="No, he doesn’t." />
+ <QaBox q="When was your daughter diagnosed with cystic fibrosis?" a="Right after birth. She was transferred to a bigger hospital due to an intestinal blockage and had surgery. After about two to three weeks in intensive care, the cystic fibrosis diagnosis came through newborn screening. At that time, the results took longer to process than they do now." />
+ <QaBox q="That intestinal issue can happen for many reasons, right?" a="Yes, it was all new to us. The beginning was difficult, but things have gotten better since then, and we’re very grateful." />
+ <QaBox q="How did you feel when you first heard the diagnosis?" a="It felt like our world was falling apart. I still remember the moment—it was like being in a movie. We were told in a separate room, and it felt overwhelming. One doctor even suggested we go home to think about it in peace, but all I could think about was returning to my child. It was a lot to take in, especially thinking about how we’d tell our family." />
+ <QaBox q="That sounds incredibly hard. How did you handle it as time passed?" a="It was tough, but we were fortunate to have a doctor who really understood what we were going through, as he had a disabled child himself. He never scared us unnecessarily and guided us step by step, which made a big difference. We know many families who live in constant fear, but since those first months, we’ve learned to manage the situation without being overwhelmed by fear." />
+ <QaBox q="Did any particular support help your family adjust to the diagnosis?" a="Yes, the rehab program we attended was a huge help. It was a family-oriented program, so my husband could be there too, which was important since I manage most things day-to-day. It really helped our daughter realize she’s not alone—she met other kids with similar conditions, which was a huge comfort." />
+ <QaBox q="How did you explain the illness to your daughter?" a="We try to give it as little attention as possible in daily life. She’s been inhaling medication since she was eight weeks old, and it’s just part of her routine now. Thankfully, she doesn’t fight it or question it much, and her school and kindergarten haven’t made a big deal of it either, which is what we wanted." />
+ <QaBox q="Does she ever ask about her illness compared to her younger brother, who doesn’t have cystic fibrosis?" a="She does sometimes ask why she’s sick and he’s not, but she’s not upset by it. We’ve made sure not to give her any special treatment because of her illness, which can be hard at times, but we want her to understand that her illness doesn’t define her." />
+ <QaBox q="That sounds like a good balance. What about medications—did she start on any special treatments?" a="Yes, she started on Orkambi at around three years old but had to stop briefly due to high liver values. Now she’s on Kaftrio, which she started shortly before her sixth birthday, and it’s been going well." />
+ <QaBox q="Did you face any issues with the health insurance for covering these medications?" a="Fortunately, no. We have statutory health insurance, and they’ve covered everything without any issues. We’ve heard it can be more complicated for those with private insurance." />
+ <QaBox q="Have you ever had difficulties with access to medication?" a="Yes, there have been times when we’ve had to wait a few days for certain medications, like Kreon or antibiotics, especially in the winter. But we always plan ahead and keep a buffer, so we’ve never been without what we need." />
+ <QaBox q="What would you say has been the most affected area for your daughter?" a="Her intestines are the most affected. Before she started Kaftrio, she had fatty stools and frequent bowel movements, even with the right Kreon dosage. Since starting Kaftrio, this has improved significantly." />
+ <QaBox q="What kind of support would you have liked to receive earlier?" a="We wish we had been given more information about available services early on. We found out about Mukoviszidose e.V. from another family, not from our doctor. It would have been helpful to know about these resources right from the start." />
+ <QaBox q="How about psychosocial support?" a="Initially, we didn’t have any psychological support—our doctor took care of everything. Now, where we live, there are more resources, and we think it’s a good thing. The rehab helped a lot in coming to terms with everything. We wish we had known about such services sooner." />
+ <QaBox q="Does your daughter do physiotherapy?" a="Yes, once a week for about an hour. She’s been going since she was discharged from the hospital, and she has a close bond with her physiotherapist. They’ve been working together since she was a baby, and she goes by herself now." />
+ <QaBox q="Are there any restrictions for her in terms of physical activities?" a="No, not really. She does dancing once a week, physiotherapy, and she’s even done a swimming course without any problems." />
+ <QaBox q="How do you handle communicating about her illness?" a="We try not to make a big deal of it. When I looked for information, I found what we needed. There’s nothing we’ve really felt was missing." />
+ </>,
+ summary: ""
},
- {
+ {
vorname: "Joshua",
- nachnname: "Bauder",
+ nachnname: "Bauder",
job: "parent and activist",
affiliation: "CF vests worldwide",
- pictureurl: pics['placeholder'],
+ pictureurl: pics['joshua'],
tag: "Patient",
heading: "Interview with a CF Parent and Global Advocate on Worldwide Support and Perspectives",
interviewtabid: "joshua",
cardtext: "",
language: "en",
quote: "We’ve had to sit by and watch people die, knowing that better treatment exists but is inaccessible. ",
- aimofcontact: [<p>We contacted the organization <a href="https://www.cfvww.org/">CF vests worldwide</a> with the aim to hear more diverse perspectives beyond Germany.
- After the founder Rod connected us with Joshua, Joshua was so kind to conduct an interview with us not only about the perspectives and
- stories he heard but also about his personal experiences with his daughter and living in a country where CF care is very hard to get. Joshua
- (from the USA) and his family live in Thailand where he and his wife run a children’s home. Their daughter is the only child with CF.</p>,
- <p>It is possible to learn more about Joshua and his family though the <a href="https://thebonnellfoundation.org/cf-vests-worldwide/">
- podcast of the Bonnel foundation</a>.</p>],
- insights: [<p> Joshua showed us just how dire the situation is for CF patients is in some regions. It was shocking to hear there is only one doctor
+ aimofcontact: [<p>We contacted the organization <a href="https://www.cfvww.org/">CF vests worldwide</a> with the aim to hear more diverse perspectives beyond Germany.
+ After the founder Rod connected us with Joshua, Joshua was so kind to conduct an interview with us not only about the perspectives and
+ stories he heard but also about his personal experiences with his daughter and living in a country where CF care is very hard to get. Joshua
+ (from the USA) and his family live in Thailand where he and his wife run a children’s home. Their daughter is the only child with CF.</p>,
+ <p>It is possible to learn more about Joshua and his family though the <a href="https://thebonnellfoundation.org/cf-vests-worldwide/">
+ podcast of the Bonnel foundation</a>.</p>],
+ insights: [<p> Joshua showed us just how dire the situation is for CF patients is in some regions. It was shocking to hear there is only one doctor
knowledgeable about CF in Thailand and that many doctors dismiss the possibility of CF due to racial bias and misinformation. Additionally, we confirmed how much the accessibility
- of care depends on the healthcare system, as we already touched on during the interview with Nicole Friedlein [link]. On the parenting level, Joshua brought in many perspectives contrary to what we previously heard. In the interview with Max [Link], we learned he vehemently avoids ponding water while Joshua’s daughter is allowed to roam around with no such restrictions. Neither have chronic infections.</p>],
- implementation: [<p>The interview with Josh made us realize we too needed to look at the reason why we chose F508del. Did we, too, fall for bias?
- Despite a change of target not being feasible anymore, we looked into it and traced back our steps that led to our decision. We did not find as much
- information about other mutations when first researching cystic fibrosis, especially in the context of prime editing. Mattijs Bulceans's paper on
- targeting the mutations L227R and N1303K <TabScrollLink tab="joshua" scrollId="desc-1" num="1" /> was one of few papers. After explicitly searching for cystic fibrosis records for specific countries and
- regions, we uncovered a moderate number of papers examining CF in Asia and other regions we previously did not know much about. The very first article
- supported Joshua's hypotheses and painted a sad picture: Among other things, it describes the case of a four-month-old boy who was diagnosed with cystic
- fibrosis. Nothing unusual in itself, but the circumstances are depressing. Two of the three siblings born before him died within months of birth and had
- previously presented with symptoms of cystic fibrosis. He was the first to be diagnosed. A sweat test aimed at cystic fibrosis was not available at the
- hospital, so one was improvised. Later on, a genetic test revealed the presence of 508del. <TabScrollLink tab="joshua" scrollId="desc-2" num="2" /> We found ourselves and our lack of knowledge in good
- company as we found papers as new as from 2020 (14 years after the previously mentioned paper) containing statements such as “recent reports suggest
- that CF does occur in Asia†<TabScrollLink tab="joshua" scrollId="desc-3" num="3" />. Fortunately, there is a rising number of cystic fibrosis experts for Asia and other previously overlooked regions
- such as Africa. <TabScrollLink tab="joshua" scrollId="desc-4" num="4" /> We chose to not only look at the scientific data but also into anecdotal evidence. To find the latter, we searched official
- and private websites and chatrooms for information and experiences of patients. In the end, we found narratives from most ethnic backgrounds
- about being dismissed and often misdiagnosed. Of course, this is not an occurrence unique to cystic fibrosis. Our conclusion is that yes,
- we did fall for bias. But regardless of ethnicity, 508del occurs and is overall the most prevalent mutation as was confirmed in our interview
+ of care depends on the healthcare system, as we already touched on during the interview with Nicole Friedlein [link]. On the parenting level, Joshua brought in many perspectives contrary to what we previously heard. In the interview with Max [Link], we learned he vehemently avoids ponding water while Joshua’s daughter is allowed to roam around with no such restrictions. Neither have chronic infections.</p>],
+ implementation: [<p>The interview with Josh made us realize we too needed to look at the reason why we chose F508del. Did we, too, fall for bias?
+ Despite a change of target not being feasible anymore, we looked into it and traced back our steps that led to our decision. We did not find as much
+ information about other mutations when first researching cystic fibrosis, especially in the context of prime editing. Mattijs Bulceans's paper on
+ targeting the mutations L227R and N1303K <TabScrollLink tab="joshua" scrollId="desc-1" num="1" /> was one of few papers. After explicitly searching for cystic fibrosis records for specific countries and
+ regions, we uncovered a moderate number of papers examining CF in Asia and other regions we previously did not know much about. The very first article
+ supported Joshua's hypotheses and painted a sad picture: Among other things, it describes the case of a four-month-old boy who was diagnosed with cystic
+ fibrosis. Nothing unusual in itself, but the circumstances are depressing. Two of the three siblings born before him died within months of birth and had
+ previously presented with symptoms of cystic fibrosis. He was the first to be diagnosed. A sweat test aimed at cystic fibrosis was not available at the
+ hospital, so one was improvised. Later on, a genetic test revealed the presence of 508del. <TabScrollLink tab="joshua" scrollId="desc-2" num="2" /> We found ourselves and our lack of knowledge in good
+ company as we found papers as new as from 2020 (14 years after the previously mentioned paper) containing statements such as “recent reports suggest
+ that CF does occur in Asia†<TabScrollLink tab="joshua" scrollId="desc-3" num="3" />. Fortunately, there is a rising number of cystic fibrosis experts for Asia and other previously overlooked regions
+ such as Africa. <TabScrollLink tab="joshua" scrollId="desc-4" num="4" /> We chose to not only look at the scientific data but also into anecdotal evidence. To find the latter, we searched official
+ and private websites and chatrooms for information and experiences of patients. In the end, we found narratives from most ethnic backgrounds
+ about being dismissed and often misdiagnosed. Of course, this is not an occurrence unique to cystic fibrosis. Our conclusion is that yes,
+ we did fall for bias. But regardless of ethnicity, 508del occurs and is overall the most prevalent mutation as was confirmed in our interview
with CF expert Sriram .... This experience was uncomfortable as we felt the pressure to be thorough and deliver a perfect project. What would
- have been more devastating than realizing we made a wrong choice at the very core? We made the conscious decision to invest our resources into
- figuring out if we indeed made a mistake and we want to encourage other teams to do the same. iGem stands for innovation – but also for growth.
- Especially in the context of Integrated Human Practices, it is important to examine both the positive and the negative to create a project with a
- future. </p>],
- pictureurl_interview: "",
+ have been more devastating than realizing we made a wrong choice at the very core? We made the conscious decision to invest our resources into
+ figuring out if we indeed made a mistake and we want to encourage other teams to do the same. iGem stands for innovation – but also for growth.
+ Especially in the context of Integrated Human Practices, it is important to examine both the positive and the negative to create a project with a
+ future. </p>],
+ pictureurl_interview: "",
references: [<ol>{/*<!-- Citation num 1--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-1">
<span property="schema:author" typeof="schema:Person">
@@ -668,7 +745,7 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>).
<a className="doi" href="https://doi.org/https://doi.org/10.1016/j.xcrm.2024.101544"> doi: https://doi.org/10.1016/j.xcrm.2024.101544</a>
</li>
-
+
{/*<!-- Citation num 2--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-2">
<span property="schema:author" typeof="schema:Person">
@@ -684,7 +761,7 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<span property="schema:pageBegin"> 1756</span>-<span property="schema:pageEnd">61</span>
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2006">2006</time>).
</li>
-
+
{/*<!-- Citation num 3--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-3">
<span property="schema:author" typeof="schema:Person">
@@ -716,7 +793,7 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2020">2020</time>).
<a className="doi" href="https://doi.org/10.4103/prcm.prcm_5_20"> doi: 10.4103/prcm.prcm_5_20</a>
</li>
-
+
{/*<!-- Citation num 4--> */}
<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-4">
<span property="schema:author" typeof="schema:Person">
@@ -733,15 +810,16 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
<a className="doi" href="https://doi.org/10.1016/j.sjbs.2023.103685"> doi: 10.1016/j.sjbs.2023.103685</a>
</li>
-
- </ol>]
+
+ </ol>],
+ summary: ""
},
- {
+ {
title: "Prof. Dr.",
vorname: "Erhard",
- nachnname: "Wischmeyer",
+ nachnname: "Wischmeyer",
job: "Research Group Cellular Neurophysiology",
- affiliation: "Universität Bielefeld",
+ affiliation: "Universität Bielefeld",
pictureurl: pics['wischmeyer'],
tag: "Academia",
heading: "Discussion on Techniques for Measuring CFTR Channel Functionality",
@@ -750,49 +828,49 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "de",
quoteNachname: "Guckes",
quoteVorname: "Isabell",
- quote: "We hadn’t initially considered patch-clamp measurements in our set of downstream applications, but it’s proven to be an exceptionally sensitive method for assessing CFTR conductance.",
+ quote: "Initially we hadn't considered patch-clamp measurements in our set of downstream applications, but it’s proven to be an exceptionally sensitive method for assessing CFTR conductance.",
aimofcontact: [<p>As part of our project, we aimed to demonstrate the functionality of the CFTR ion channel, after restoring
it through our optimized Prime Editing, by using Patch-Clamp measurements. To ensure the optimal use of the
- Patch-Clamp and to gain an insight into electrophysiology, we asked experts from the medical faculty at
- Bielefeld University to critically examine our measurement planning. Prof. Dr. Erhard Wischmeyer, an
- experienced scientist in this field who has worked at the Max Planck Institute for Biophysical Chemistry
- in Göttingen, the development site of the Patch-Clamp technique<ScrollLinkWithChild targetId="desc-1"><sup>1</sup></ScrollLinkWithChild>, and currently leads the Cellular
- Neurophysiology working group at Bielefeld University, seemed to be an ideal interviewee. His
- knowledge and experience promised valuable insights and advice for conducting and optimizing our
- experiments. </p>],
- insights: [ <><p>Prof. Dr. Wischmeyer taught us about the workflow of the Patch-Clamp technique. He highlighted the need
- for specialized electrodes and glass pipettes that must form a smooth surface devoid of the extracellular
- matrix (ECM). Additionally, he pointed out that measuring CFTR conductivity with the Patch-Clamp technique
- poses a technical challenge due to the low currents involved<ScrollLinkWithChild targetId="desc-2"><sup>2</sup></ScrollLinkWithChild>. He recommended using expression vectors
- for overexpressing the CFTR gene in HEK cells instead of epithelial cells from a nasal swab to achieve
- better results. Since Patch-Clamp measurements require a very sensitive testing environment, even
- challenging for the most experienced scientists, Prof. Dr. Wischmeyer invited us to conduct the
- measurements together with members of his group.
+ Patch-Clamp and to gain an insight into electrophysiology, we asked experts from the medical faculty at
+ Bielefeld University to critically examine our measurement planning. Prof. Dr. Erhard Wischmeyer, an
+ experienced scientist in this field who has worked at the Max Planck Institute for Biophysical Chemistry
+ in Göttingen, the development site of the Patch-Clamp technique<ScrollLinkWithChild targetId="desc-1"><sup>1</sup></ScrollLinkWithChild>, and currently leads the Cellular
+ Neurophysiology working group at Bielefeld University, seemed to be an ideal interviewee. His
+ knowledge and experience promised valuable insights and advice for conducting and optimizing our
+ experiments. </p>],
+ insights: [<><p>Prof. Dr. Wischmeyer taught us about the workflow of the Patch-Clamp technique. He highlighted the need
+ for specialized electrodes and glass pipettes that must form a smooth surface devoid of the extracellular
+ matrix (ECM). Additionally, he pointed out that measuring CFTR conductivity with the Patch-Clamp technique
+ poses a technical challenge due to the low currents involved<ScrollLinkWithChild targetId="desc-2"><sup>2</sup></ScrollLinkWithChild>. He recommended using expression vectors
+ for overexpressing the CFTR gene in HEK cells instead of epithelial cells from a nasal swab to achieve
+ better results. Since Patch-Clamp measurements require a very sensitive testing environment, even
+ challenging for the most experienced scientists, Prof. Dr. Wischmeyer invited us to conduct the
+ measurements together with members of his group.
</p>
- <p>In addition to the Patch-Clamp technique, Prof. Dr. Wischmeyer informed us about E-cis measurements as a
- current electrophysiological measurement method alongside the Patch-Clamp technique. This method allows
- the measurement of the membrane potential above and below a monolayer of confluent cells<ScrollLinkWithChild targetId="desc-3"><sup>3</sup></ScrollLinkWithChild>. Consequently,
- it enables precise measurement of conductivity dependent on CFTR expression. </p>
- </>],
- implementation: [<> <p>We decided to use HEK293T cells lines from Mattijs Bulcaen from KU Leuven [Link] which do overexpress the
- correct CFTR and those which express CFTR with F508del for the Patch-Clamp measurements. To conduct the
- Patch-Clamp experiments, we contacted the Cellular Neurophysiology group to perform the necessary
- measurements. It was a pleasure to work together with Dr. Oliver Dräger[Link], who is working as a post-doc for
- the Cellular Neurophysiology working group at Bielefeld University. He taught us about the Patch-Clamp
- method and spent his valuable time supporting our project by guiding our Patch-Clamp measurements. </p>
- <p>In summary, through the interview with Prof. Dr. Wischmeyer and the collaboration with his employee
- Oliver Dräger, we gained valuable insights and optimized our approach to effectively investigate and
- measure the functionality of the CFTR ion channel, thereby determining the efficiency of our Prime
- Editing strategy. </p></>],
+ <p>In addition to the Patch-Clamp technique, Prof. Dr. Wischmeyer informed us about E-cis measurements as a
+ current electrophysiological measurement method alongside the Patch-Clamp technique. This method allows
+ the measurement of the membrane potential above and below a monolayer of confluent cells<ScrollLinkWithChild targetId="desc-3"><sup>3</sup></ScrollLinkWithChild>. Consequently,
+ it enables precise measurement of conductivity dependent on CFTR expression. </p>
+ </>],
+ implementation: [<> <p>We decided to use HEK293T cells lines from Mattijs Bulcaen from KU Leuven [Link] which do overexpress the
+ correct CFTR and those which express CFTR with F508del for the Patch-Clamp measurements. To conduct the
+ Patch-Clamp experiments, we contacted the Cellular Neurophysiology group to perform the necessary
+ measurements. It was a pleasure to work together with Dr. Oliver Dräger[Link], who is working as a post-doc for
+ the Cellular Neurophysiology working group at Bielefeld University. He taught us about the Patch-Clamp
+ method and spent his valuable time supporting our project by guiding our Patch-Clamp measurements. </p>
+ <p>In summary, through the interview with Prof. Dr. Wischmeyer and the collaboration with his employee
+ Oliver Dräger, we gained valuable insights and optimized our approach to effectively investigate and
+ measure the functionality of the CFTR ion channel, thereby determining the efficiency of our Prime
+ Editing strategy. </p></>],
pictureurl_implementation: "https://static.igem.wiki/teams/5247/photos/for-wiki-texts/hp-patch-clamp/bild-interssierte-wissenschaftler-oho.jpeg",
pictureurl_aim: "https://static.igem.wiki/teams/5247/photos/for-wiki-texts/hp-patch-clamp/20240625-184032.jpg",
references: [
<ol>
- {/*<!-- Citation num 1--> */}
- <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="bielefeld-cebitec/human-practices#desc-1">
+ {/*<!-- Citation num 1--> */}
+ <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="bielefeld-cebitec/human-practices#desc-1">
<span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Roth, F.</span>;
- <span property="schema:Name"> Draguhn, A.</span>
+ <span property="schema:Name"> Roth, F.</span>;
+ <span property="schema:Name"> Draguhn, A.</span>
</span>
<span property="schema:name"> Die Entwicklung der Patch-Clamp-Technik. </span>
<i property="schema:publisher" typeof="schema:Organization"> Springer eBooks</i>
@@ -800,12 +878,12 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<span property="schema:pageBegin"> 1</span>-<span property="schema:pageEnd">14</span>
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
<a className="doi" href="https://doi.org/10.1007/978-3-662-66053-9_1"> doi: 10.1007/978-3-662-66053-9_1</a>
- </li>
-
- {/*<!-- Citation num 2--> */}
- <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-2">
+ </li>
+
+ {/*<!-- Citation num 2--> */}
+ <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-2">
<span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Mete, V.</span>
+ <span property="schema:Name"> Mete, V.</span>
</span>
<span property="schema:name"> Entwicklung und Validierung neuer nicht-invasiver Diagnosesysteme für Mucociliary Clearance Disorders (MCCD). </span>
<i property="schema:publisher" typeof="schema:Organization"> Dissertation, Westfälische Wilhelms-Universität Münster</i>
@@ -813,13 +891,13 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<span property="schema:pageBegin"> </span>
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>).
<a className="doi" href="https://doi.org/10.17879/98958441905"> doi: 10.17879/98958441905</a>
- </li>
-
- {/*<!-- Citation num 3--> */}
- <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-3">
+ </li>
+
+ {/*<!-- Citation num 3--> */}
+ <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-3">
<span property="schema:author" typeof="schema:Person">
- <span property="schema:Name"> Giaever, I.</span>;
- <span property="schema:Name"> Keese, C.</span>
+ <span property="schema:Name"> Giaever, I.</span>;
+ <span property="schema:Name"> Keese, C.</span>
</span>
<span property="schema:name"> A morphological biosensor for mammalian cells. </span>
<i property="schema:publisher" typeof="schema:Organization"> Nature</i>
@@ -827,17 +905,18 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<span property="schema:pageBegin"> 591</span>-<span property="schema:pageEnd">592</span>
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 1993">1993</time>).
<a className="doi" href="https://doi.org/10.1038/366591a0"> doi: 10.1038/366591a0</a>
- </li>
+ </li>
</ol>
],
+ summary: ""
},
- {
+ {
title: "Prof. Dr.",
vorname: "Stefan",
- nachnname: "Hammer",
+ nachnname: "Hammer",
job: "Junior Professor of Organic Chemistry and Biocatalysis",
- affiliation: "Universität Bielefeld",
- pictureurl: pics['placeholder'],
+ affiliation: "Universität Bielefeld",
+ pictureurl: pics['hammer'],
tag: "Academia",
heading: "Safety Briefing and Laboratory Practices Advice",
interviewtabid: "hammer",
@@ -845,16 +924,17 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "de",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
+ summary: ""
},
- {
+ {
title: "Dr.",
vorname: "Katharina",
- nachnname: "Kolonko",
+ nachnname: "Kolonko",
job: "",
- affiliation: "",
+ affiliation: "",
pictureurl: pics['kolonko'],
tag: "Academia",
heading: "First steps in LNPs",
@@ -863,15 +943,16 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "de",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
+ summary: ""
},
- {
+ {
vorname: "Svenja",
- nachnname: "Vinke",
+ nachnname: "Vinke",
job: "PostDoc at Harvard Medical School",
- affiliation: "Harvard Medical School",
+ affiliation: "Harvard Medical School",
pictureurl: pics['svenja'],
tag: "Academia",
heading: "",
@@ -879,14 +960,22 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
language: "de",
quote: "",
- aimofcontact: "",
-
- insights: "",
- implementation: "",
+ aimofcontact: [<p>We contacted Svenja Vinke, a former iGEMer from Bielefeld, to get her insight and her opinion regarding the use of phage assisted continuous evolution
+ (PACE, see engineering cycle 1[Link]) for our prime editing optimizations. Svenja works at the iGEM Safety and Security Committee. Additionally, she was part of the Biosafety and Security Award Team of Bielefeld University in 2016.</p>],
+ insights: [<p>Svenja explained, that a PACE approach is not feasible to use for optimization of our nickase candidates because of several reasons:</p>,
+ <ul>
+ <li>Implementing a PACE system takes way too much time to use for our project.</li>
+ <li>Endonucleases might be too big to optimize using PACE.</li>
+ <li>Unspecific cutting or nicking in the bacterial genome kills the cells, which makes optimization of endonucleases very challenging.</li>
+ <li>Prime editing in E. coli cells is less effective compared to human cells, which might impair the evolution process.</li>
+ </ul>
+ ],
+ implementation: [<p>On the basis of Svenja’s and other opinions on the topic, we decided not to try implementing a PACE system. </p>],
+ summary: ""
},
- {
+ {
vorname: "Max",
- nachnname: "Beckmann",
+ nachnname: "Beckmann",
job: "Bielefeld University",
pictureurl: pics['max'],
tag: "Patient",
@@ -898,29 +987,31 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
+ summary: ""
},
- {
+ {
title: "Dr.",
vorname: "Eva-Maria",
- nachnname: "Berens",
+ nachnname: "Berens",
job: "Ethics Committee of Bielefeld University",
- affiliation: "Bielefeld University",
+ affiliation: "Bielefeld University",
pictureurl: pics['berens'],
tag: "Academia",
heading: "Bioethics: Best Practices for Handling Patient Data and Primary Cells", /* Guidance from Ethics Committee on Best Practices for Patient Data and Primary Cells */
interviewtabid: "berens",
cardtext: "",
language: "de",
- quote: "",
+ quote: "The most important thing is a detailed letter of consent and a detailed privacy policy. This must explain to the patient as precisely as possible what happens to their cells and data, as well as the time span, which people are involved or have access to the cells and how.",
aimofcontact: "The aim of the interview was to get an answer to the question of whether we need an ethics vote for our project or not and to obtain guidelines for dealing with patient cells regarding ethical issues and data protection. ",
insights: "The discussion was very informative in terms of how we should approach this topic and focused primarily on the important factors that need to be considered when planning the handling of patient cells. These include which legal principles need to be observed, data protection, ethical considerations and, above all, detailed and specific information for the donor. It also made us look at the situation from many different angles and consider the risks of worst-case scenarios. Overall, this interview was very useful to us, and we were able to use the information we gained to develop a kind of guideline that allowed us to approach this sensitive topic, which was new to us, with a certain degree of confidence. ",
implementation: "Based on the knowledge we have gained, we have drawn up guidelines for our handling of the cells. We used this guide when handling the patient cells, to ensure they were handled in an ethically correct manner.",
+ summary: ""
},
- {
+ {
vorname: "Collaboration",
- nachnname: "",
+ nachnname: "",
job: "",
- affiliation: "",
+ affiliation: "",
pictureurl: pics['placeholder'],
tag: "Academia",
heading: "LNP Handbook",
@@ -931,13 +1022,14 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
aimofcontact: "",
insights: "",
implementation: "",
+ summary: ""
},
- {
+ {
vorname: "Benjamin",
title: "Dr.",
- nachnname: "Winkeljann",
+ nachnname: "Winkeljann",
job: "Co-Founder and CEO at RNhale",
- affiliation: "RNhale",
+ affiliation: "RNhale",
pictureurl: pics['winkeljann'],
tag: "Industry",
heading: "Rnhale",
@@ -945,30 +1037,30 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
cardtext: "",
language: "de",
quote: "Spray-drying LNPs is a groundbreaking approach that enhances stability and enables efficient pulmonary delivery of mRNA, paving the way for innovative therapies for conditions like cystic fibrosis.",
- aimofcontact: [<p>As part of our development process of an innovative, effective pulmonary delivery of therapeutic mRNA to fight cystic fibrosis,
- we conducted an interview with Dr. Benjamin Winkeljann, who is the Co-Founder of <a href="https://rnhale.com/">RNhale</a>. Dr. Benjamin
+ aimofcontact: [<p>As part of our development process of an innovative, effective pulmonary delivery of therapeutic mRNA to fight cystic fibrosis,
+ we conducted an interview with Dr. Benjamin Winkeljann, who is the Co-Founder of <a href="https://rnhale.com/">RNhale</a>. Dr. Benjamin
Winkeljann has a wealth of experience in the field of RNA therapeutics and nanotechnology. His background includes extensive research in the
- development of lipid-based delivery systems, focusing on optimizing stability and efficacy for therapeutic applications. Winkeljann’s work
- is supported by cutting-edge research from academic institutions, including collaborations with Professor Olivia Merkel from the
- Ludwig-Maximilians-Universität in Munich, Germany, since his doctoral thesis in her working group. The interview with Winkeljann promoted
- our project, which aimed to utilize spray-dried lipid nanoparticles (LNPs) for efficient delivery to the lung. By engaging with RNhale, we
- sought to understand the nuances of their nano-embedded microparticle technology and how it could enhance our delivery systems. </p>],
- insights: [<p>RNhale's technology leverages advanced spray drying techniques to stabilize and deliver RNA therapeutics. During our interview,
- Winkeljann detailed several crucial aspects. Firstly, the stability and shelf-life of spray-dried LNPs are remarkable. RNhale’s siRNA
- formulations have maintained their integrity for up to 18 months at room temperature, and although specific data for mRNA is still pending,
+ development of lipid-based delivery systems, focusing on optimizing stability and efficacy for therapeutic applications. Winkeljann’s work
+ is supported by cutting-edge research from academic institutions, including collaborations with Professor Olivia Merkel from the
+ Ludwig-Maximilians-Universität in Munich, Germany, since his doctoral thesis in her working group. The interview with Winkeljann promoted
+ our project, which aimed to utilize spray-dried lipid nanoparticles (LNPs) for efficient delivery to the lung. By engaging with RNhale, we
+ sought to understand the nuances of their nano-embedded microparticle technology and how it could enhance our delivery systems. </p>],
+ insights: [<p>RNhale's technology leverages advanced spray drying techniques to stabilize and deliver RNA therapeutics. During our interview,
+ Winkeljann detailed several crucial aspects. Firstly, the stability and shelf-life of spray-dried LNPs are remarkable. RNhale’s siRNA
+ formulations have maintained their integrity for up to 18 months at room temperature, and although specific data for mRNA is still pending,
this suggests a promising shelf-life for mRNA formulations under similar conditions. The spray drying process itself involves mixing an ethanol
- phase containing lipids with an aqueous phase containing RNA. This mixture is then spray-dried, forming LNPs as tiny spherical particles.
- Key parameters for this process include maintaining an internal drying temperature of around 100 °C and using excipients like lactose to
- preserve the nanoparticles' structure and function​ <TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />. </p>,
- <p>Ensuring the integrity and efficiency of the LNPs involves various methods, including gel electrophoresis, blotting, and functional readouts through transfection assays.
+ phase containing lipids with an aqueous phase containing RNA. This mixture is then spray-dried, forming LNPs as tiny spherical particles.
+ Key parameters for this process include maintaining an internal drying temperature of around 100 °C and using excipients like lactose to
+ preserve the nanoparticles' structure and function​ <TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />. </p>,
+ <p>Ensuring the integrity and efficiency of the LNPs involves various methods, including gel electrophoresis, blotting, and functional readouts through transfection assays.
After drying, the nanoparticles retain their spherical structure, which resembles that of "golf balls" under scanning electron microscopy (SEM)<TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />.
- Moreover, RNhale employs artificial intelligence to optimize LNP formulations and predict the best drying conditions, reducing the need for
- extensive wet lab work. This AI-driven approach enhances efficiency and reliability in developing therapeutic nanoparticles. </p>],
+ Moreover, RNhale employs artificial intelligence to optimize LNP formulations and predict the best drying conditions, reducing the need for
+ extensive wet lab work. This AI-driven approach enhances efficiency and reliability in developing therapeutic nanoparticles. </p>],
implementation: [
- <p>The interview with Dr. Benjamin Winkeljann from RNhale provided invaluable insights that will significantly enhance our project
- focused on mRNA delivery to the lungs using spray-dried LNPs. By seeking to integrate their proven techniques and innovative approach
- to spray-dry LNPs, we are optimistic about achieving superior stability, efficacy, and scalability in our therapeutic delivery systems. </p>
- ],
+ <p>The interview with Dr. Benjamin Winkeljann from RNhale provided invaluable insights that will significantly enhance our project
+ focused on mRNA delivery to the lungs using spray-dried LNPs. By seeking to integrate their proven techniques and innovative approach
+ to spray-dry LNPs, we are optimistic about achieving superior stability, efficacy, and scalability in our therapeutic delivery systems. </p>
+ ],
pictureurl_aim: "https://static.igem.wiki/teams/5247/photos/hp/hp-rnhale-zoom.png",
pictureurl_interview: "https://static.igem.wiki/teams/5247/photos/for-wiki-texts/del-interview-rnhale/paper-overview.jpg",
pictureurl_implementation: "https://static.igem.wiki/teams/5247/photos/for-wiki-texts/del-interview-rnhale/paper-sem.jpg",
@@ -996,45 +1088,56 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
(<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2022">2022</time>).
<a className="doi" href="https://doi.org/https://doi.org/10.1016/j.jconrel.2022.09.021"> doi: https://doi.org/10.1016/j.jconrel.2022.09.021</a>
</li>
-
- </ol>]
+
+ </ol>],
+ summary: ""
},
- {
+ {
title: "XXX",
vorname: "David",
- nachnname: "Liu",
+ nachnname: "Liu",
job: "",
- affiliation: "",
+ affiliation: "",
pictureurl: pics['placeholder'],
tag: "Academia",
- heading: "",
+ heading: "Influence of research by David Liu on our design decisions ",
interviewtabid: "liu",
cardtext: "",
quote: "",
aimofcontact: "",
insights: "",
implementation: "",
+ summary: ""
},
- {
- vorname: "",
- nachnname: "",
- job: "",
- affiliation: "Corden Pharma",
+ {
+ vorname: "Steffen Bira and",
+ nachnname: "Serra Gürcan from Corden Pharma",
+ job: "Associate director",
+ affiliation: "Corden Pharma",
pictureurl: pics['placeholder'],
tag: "Industry",
- heading: "Corden",
+ heading: "Lipid Nanoparticles in Gene Therapy: perspectives from Corden Pharma ",
interviewtabid: "corden",
cardtext: "",
language: "de",
quote: "",
- aimofcontact: "",
-
- insights: "",
- implementation: "",
+ aimofcontact: [<p>The goal of the discussion with Steffen Bira and Serra Gürcan from Corden Pharma was to gain insight into the design, stability, and practical application of lipid nanoparticles (LNPs) for use in gene therapy. The conversation focused on the possibility of using Corden Pharma’s LNP starter kits, understanding the factors affecting the stability of LNPs, and exploring options for incorporating antibodies into LNPs to target specific cells. </p>],
+ insights: [<p>Steffen Bira and Serra Gürcan of Corden Pharma[Link Corden Pharmahttps://cordenpharma.com/] indicated that our planned spray drying approach of LNPs has not been extensively explored within their operations. The company focuses primarily on the aseptic fill and finish of LNPs, particularly for injectable formulations. However, they acknowledged the potential for spray drying and recommended consulting with specialized companies to assess the feasibility.
+ The stability of the lipids used in LNPs during the spray drying process was also identified as an area requiring further investigation.
+ The stability of LNPs, in particular in the context of the shear forces encountered in inhalation therapy, was identified as a critical factor. Corden Pharma highlighted that while the stability of individual lipid components can be evaluated, the stability of a complete LNP formulation containing RNA or other payloads must be empirically tested. The company put forward the suggestion that cryoprotectants and varying temperature conditions might be considered to
+ enhance the stability of LNPs during processing. Corden Pharma outlined the process used to select the lipids included in their LNP starter kits, nothing that these combinations are based on established interactions and research findings, particularly in RNA-containing formulations. The kits are designed to facilitate the creation of stable LNPs by providing materials that have been tested for their physical-chemical properties, encapsulation efficiency, and potency. Furthermore, the company highlighted that a single LNP starter kit can be used for multiple batches, offering a practical solution for experimental work.
+ When asked about modifying lipid components within LNP formulations, Corden Pharma suggested that exploring alternative lipids and other components could be beneficial for improving stability and efficacy, depending on the specific needs of the project. We discussed the availability of various lipids, including derivatives of cholesterol, which might enhance transfection efficiency in certain cell types. Corden Pharma confirmed that it is also possible to incorporate antibodies into LNPs, either during the initial preparation phase or by incubating antibodies with formed LNPs to achieve surface localization.
+ While they did not have hands-on experience in this specific application, they referenced existing studies that could provide further guidance.
+ Corden Pharma clarified that their role as a Contract Development and Manufacturing Organization (CDMO) is focused on providing services
+ for the production of active pharmaceutical ingredients (APIs) and excipients, rather than developing therapeutic products. They advised that intellectual property (IP) considerations are crucial when selecting lipids for LNP formulations, especially in commercial applications, as many lipids are patented. Companies pursuing gene therapy projects should ensure that the lipids they choose are free from IP restrictions or be prepared to pay associated fees.
+ The possibility of establishing a collaborative relationship was discussed, with Corden Pharma open to the idea of offering discounts on LNP starter kits or other materials in exchange for recognition in publications or other forms of acknowledgment. This proposal is subject to internal approval and would be pursued further through direct communication. </p>],
+ implementation: [<p>The cooperation with Cordon Pharma provided invaluable insights for the project, particularly regarding the selection of lipids critical LNP stability and the potential applications of LNPs in gene therapy. Our initial approach involved utilising the Cayman kit, which proved to be suboptimal for the intended delivery of our Primeguide. The Corden Pharma kit #2 offers enhanced delivery efficiency thanks to its cutting-edge lipid components, including cationic lipids that boost cellular uptake and auxiliary lipids
+ that reinforce the LNP structure. However, we have subsequently updated our approach and now use the Corden Pharma Kit, which builds on these benefits by including even more optimised lipid formulations. This change allows us to further improve the robustness and stability of our LNP formulations. The insights gained from the survey will significantly influence our testing process and enable us to optimise the delivery of therapeutic agents and improve overall treatment efficacy. </p>],
+ summary: ""
},
- {
+ {
vorname: "Mattijs",
- nachnname: "Bulcaen",
+ nachnname: "Bulcaen",
job: "PhD Researcher at Laboratory for Molecular Virology & Gene Therapy",
affiliation: "KU Leuven",
pictureurl: pics['mattijs'],
@@ -1045,16 +1148,17 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "en",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
+ summary: ""
},
- {
+ {
title: "Dr.",
vorname: "Oliver",
- nachnname: "Dräger",
+ nachnname: "Dräger",
job: "Bielefeld University",
- affiliation: "Research Group Cellular Neurophysiology",
+ affiliation: "Research Group Cellular Neurophysiology",
pictureurl: pics['draeger'],
tag: "Academia",
heading: "",
@@ -1063,9 +1167,245 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "de",
quote: "",
aimofcontact: "",
-
+
insights: "",
implementation: "",
+ summary: ""
},
+ {
+ title: "",
+ vorname: "Nils",
+ nachnname: "Berelsmann",
+ job: "",
+ affiliation: "University of Bielefeld",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "Focus on adapting expression strategies for Fanzor nickases and exploring the potential of Pichia pastoris (SMD1163) for SpuFz1 nickase variants ",
+ interviewtabid: "nberelsmann",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "Michael",
+ nachnname: "Johannfunke",
+ job: "Representative body for severely disabled persons",
+ affiliation: "University Bielefeld",
+ pictureurl: pics['johannfunke'],
+ tag: "Academia",
+ heading: "urgent requirement for a hygiene concept for students with disabilities and immunocompromised employees ",
+ interviewtabid: "johannfunke",
+ cardtext: "",
+ quote: "The implementation of the hygiene concept is proving more difficult than expected due to the bureaucracy at the university. Nevertheless, the interview gave us a good insight into this labyrinth of regulations and we got started the prozess of implementation.",
+ quoteVorname: "Vera",
+ quoteNachname: "Köhler",
+ aimofcontact: [<p>We contacted the university because of the urgent need to address the issue of hygiene for students and staff, particularly those with immunocomprised students and staff. There was a need to develop an effective hygiene concept to ensure the health and safety of these people. We developed this concept in collaboration with Max, our CF friend. [Link] </p>],
+ insights: [<p>We learnt that our hygiene concept is very well-developed. But although a well-developed hygiene concept is already existing, strategic development and a step-by-step approach are needed. In particular, the step-by-step implementation was emphasized, like starting with equipping the toilets. Bureaucratic hurdles, such as the need to apply to the rectorate, were identified as a major challenge. In addition, it became clear that there is a great need for sanitary facilities and facilities for the disabled, especially due to the needs of students and staff with health problems. Interaction and networking with other universities was also considered valuable. </p>],
+ implementation: [<p>The next phase of developing a new hygiene concept is to maintain contact with Mr. Johannfunke in order to continue to advance the hygiene concept in collaboration. The strategic approach entails the incremental implementation of measures, exemplified by the establishment of the inaugural toilet facility within the main building. It is of the utmost importance to ensure the uninterrupted implementation of the hygiene concept. In order to achieve this, it is essential to draw upon the existing plans and measures that have already been implemented in new buildings. We are working on advancing the plans at a higher level and are in regular dialogue with the Central contact point Barrier-free in order to overcome bureaucratic hurdles and actively promote the topic. Furthermore, it is necessary to intensify lobbying work in order to gain greater support for this issue at both the university and political levels. </p>],
+ interview: <>
+ <QaBox q="What do you think of our hygiene concept and our plan?" a="This is a very acute problem. It particularly affects students with disabilities and immune-compromised staff, such as those with cancer or cystic fibrosis, who are forced to work from home. The problem is: Employees can work from home, but students cannot. There is a great need for hygiene measures, as contact must be avoided to minimise the risk of infection."/>
+ <QaBox q="What are the challenges in implementing the hygiene concept?" a="There is a lack of strategic development, although your hygiene concept is well developed. It is necessary to proceed in small steps, e.g. starting with a toilet in the main building. However, bureaucracy is a major obstacle. To be implemented, an application has to be submitted to the rectorate, and these processes are often lengthy and complicated."/>
+ <QaBox q="What is the current situation at our university?" a="While some progress has been made with the installation of additional toilets and disabled-friendly toilets in new buildings, there is as yet no overarching strategy in place to guide future developments. Furthermore, the lack of clarity regarding the mission statement and objectives leaves room for ambiguity. The duty of care that employers have towards employees is established, yet the situation is regulated differently with regards to students. The possibility of receiving compensation for disadvantages is open, but is frequently seen as inadequate."/>
+ <QaBox q="What are the next steps in implementing the hygiene concept?" a="It is essential that the concept be implemented in small, strategic steps. At the same time, it is vital that the rectorate and other decision-makers be consulted on a regular basis to ensure that this matter remains at the forefront of discussions. Furthermore, it is of great importance to engage in political lobbying to secure additional support for this issue."/>
+ </>,
+ summary: "We got in touch because there was an acute hygiene problem for particularly vulnerable groups like immunocomprised persons at the university. We learnt from the exchange that despite a well-developed hygiene policy, strategic steps are still needed, especially to overcome bureaucratic hurdles. We have integrated these lessons into our project by focusing on continuous collaboration with the Central contact point Barrier-free and other decision-makers."
+ },
+ {
+ title: "Dr.",
+ vorname: "Sriram",
+ nachnname: "Vaidyanathan ",
+ job: "Principle investigator at Nationwide Children’s Hospital and assistant professor Pediatric’s at the Ohio State University College of Medicine ",
+ affiliation: "Nationwide Children’s Hospital",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "F508del mutation confirmed as the most common CFTR mutation worldwide, including Asia, supporting the efficacy of existing therapies for the majority of patients. ",
+ interviewtabid: "sriram",
+ language: "en",
+ cardtext: "",
+ quote: "I think you're thinking about it the right way.[...] I would have talked to all of the exact people that you have already spoken with.",
+ aimofcontact: [<p>The objective of this contact was to gather further information about cystic fibrosis (CF) in Asia, with a particular focus on understanding potential data biases, identifying common mutations, exploring the available medications, and assessing the diagnostic practices in the region. </p>],
+ insights: [<p>The talk with Sriram revealed that, although cystic fibrosis (CF) is relatively uncommon in Asia compared to other disease like sickle cell disease, it nevertheless exhibits considerable genetic diversity. The identification of different mutations in the CFTR gene across the region has revealed that the F508del mutation is the most common, a finding that aligns with global patterns. However, in Asian populations, other rare mutations are also prevalent, which presents unique challenges in diagnosis and treatment.
+ Additionally, it was found that environmental factors, such as air pollution, serve to exacerbate the symptoms of CF, particularly in densely populated regions, thereby further complicating the management of the disease. This emphasises the necessity for further research on CF that is specifically tailored to the needs of different regions, including improvements in diagnostic techniques and the development of treatments that are more closely aligned with the characteristics of the populations in question. </p>],
+ implementation: [<p>The data were incorporated by confirming that the F508del mutation is not only the most common in Europe but also globally, including in Asia, highlighting a broader perspective and contributing to a significant horizon expansion in understanding the mutation's worldwide prevalence. This finding lends support to the idea that existing therapies targeting the F508del mutation will be effective for many patients worldwide, thereby providing a solid foundation for treatment. As a starting point, this is promising, but future efforts will focus on adapting therapies to address other, rarer mutations found in specific populations.
+ </p>],
+ summary: "The contact provided valuable insights into cystic fibrosis (CF) in Asia and confirmed that the F508del mutation is the most common, as it is globally. However, the genetic diversity observed in Asia, together with the exacerbation of symptoms by environmental factors such as air pollution, highlights the need for more region-specific research. Future efforts will focus on refining treatments for rarer mutations and improving diagnostic accuracy in Asian populations.",
+ },
+ {
+ title: "",
+ vorname: "Philipp",
+ nachnname: "Kühnel",
+ job: "PhD student in the Otorhinolaryngology working group at Bielefeld University",
+ affiliation: "Universität Bielefeld",
+ pictureurl: pics['kühnel'],
+ tag: "Academia",
+ heading: "Philipp Kühnel’s guidance significantly improved our culture protocols and experimental outcomes, particularly in maintaining ALI cultures and addressing fungal contamination issues.",
+ interviewtabid: "pkuehnel",
+ cardtext: "",
+ quote: "x",
+ aimofcontact: [<p>The aim of our contact with Philipp Kühnel, a PhD student from the Otorhinolaryngology working group of Bielefeld University, was to gain expertise in working with primary cultures, particularly focusing on air-liquid interface (ALI) cultures. Given his experience in this area, we sought his guidance to ensure that we were following best practices and to address any technical challenges we might encounter.</p>],
+ insights: [<p>Through our discussions with Philipp, we gained valuable insights into the optimal conditions for cultivating primary cells and maintaining ALI cultures. He provided practical advice on troubleshooting of common issues, such as cell differentiation and culture stability, which were crucial for the success of our experiments. We also maintained close contact to exchange information about fungi that frequently contaminate ALI cultures. The expertise shared on combating these fungal contaminations was particularly valuable and greatly enhanced our understanding of effective prevention and treatment methods. </p>],
+ implementation: [<p>We incorporated Philipp’s advice by refining our culture protocols, particularly adjusting the conditions for ALI cultures to improve cell differentiation and overall culture health. This directly enhanced the reliability of our experimental results, ensuring that our work with primary cultures was both accurate and reproducible. </p>],
+ summary: "The contact aimed to leverage Philipp’s expertise in ALI cultures to improve our experimental protocols Gained insights into optimizing conditions for primary cell cultures and managing common challenges like fungal contamination"
+ },
+ {
+ title: "",
+ vorname: "Timm",
+ nachnname: "Weber",
+ job: "Quality Manager | Immunologist",
+ affiliation: " Biobank OWL (Bielefeld and Lippe)",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "Discussed the processes involved in the storage, processing, and security of patient samples.",
+ interviewtabid: "timm",
+ cardtext: "",
+ quote: "A biobank is not just a collection of samples; it's a bridge between patient trust and scientific discovery, ensuring that valuable biological data is safeguarded while contributing to future research.",
+ aimofcontact: "Contact was established with Timm for the purpose of gaining deeper insights into the functioning of the biobank and of deepening our understanding of the processing of patient samples.",
+ insights: "We were provided with invaluable insights into the quality and project management of the biobank and storage of patient samples. It was of particular interest to note that Biobank OWL occupies a distinctive position in this context, insofar as a trustee is not a mandatory figure within its system and is therefore not provided for as a standard component. However, Biobank OWL has elected to integrate a trustee in order to enhance the security standards for the safeguarding of patient data. This illustrates the biobank's dedication to ensuring the optimal protection and security of sensitive patient data.",
+ implementation: "The insights gained have facilitated a deeper comprehension of the significance of quality management in the processing of patient samples. This understanding has been integrated into our project processes, thereby enhancing the accuracy and reliability of our procedures. ",
+ summary: "The interview focused on understanding the operations of the Biobank OWL, particularly in the areas of quality management and sample processing. Provided a detailed overview of biobank activities, including sample collection, storage conditions, and data protection measures",
+ interview: <>
+ <QaBox q="Can you briefly explain to us what exactly a biobank is and what its main tasks are?"
+ a="A biobank is a specialized facility that collects, stores, and manages biological samples and associated data for research purposes. Each biobank is unique in its operations and functions. In Bielefeld and Lippe, the Biobank BOWL (Biobank OWL) is responsible for the storage of patient samples. The Data Integration Centre (DIZ) stores data pertaining to these samples. A trustee oversees the pseudonymisation of data, acting as an interface between BOWL and DIZ, ensuring that patient data cannot be directly linked to patient samples." />
+ <QaBox q="What types of samples are collected in your biobank and for what research purposes are they used?"
+ a="The biobank collects a wide variety of samples, including blood, stool, and soil. Samples may be gathered for specific research projects or for establishing a general repository under 'broad consent.' Researchers wishing to use these samples must apply to the 'use access committee,' which evaluates whether the requested samples and data can be released for their research." />
+ <QaBox q="How large is your biobank? How many samples do you currently store and how many new samples are added on average?"
+ a="The biobank is still in the process of establishing itself and has not yet reached its full sample capacity. However, it is anticipated to accumulate a significant number of samples in the near future, with several thousand samples expected to be analyzed in dedicated sessions." />
+ <QaBox q="What requirements and criteria must be met for a sample to be included in your biobank?"a="Samples must be processed according to highly detailed protocols, and regular audits are conducted to ensure compliance with all standards." />
+ <QaBox q="Which other research institutions or biobanks do you cooperate with and what form does this cooperation take?"
+ a="Biobank OWL has a second location in Lippe, in addition to Bielefeld. Collaborations exist with the DIZ, the Treuhand, and three university hospitals. It is anticipated that cooperation with other working groups will increase in the future." />
+ <QaBox q="What specific storage conditions (e.g. temperature, humidity) must be observed for different sample types?"
+ a="Samples are stored under various temperature conditions, including -20°C, -80°C, and -150°C, along with the use of liquid nitrogen." />
+ <QaBox q="How do you ensure that the samples remain stable and usable over longer periods of time?"
+ a="Samples are stored in nitrogen for long-term stability." />
+ <QaBox q="What encryption techniques or data protection measures are used in your biobank to prevent unauthorized access to patient data? Are there special regulations for the anonymisation of data and how is it ensured that patients cannot be traced?"
+ a="Pseudonyms are created using specialized software such as CentraXX or REDcap to protect patient data." />
+ <QaBox q="What rights do patients have in relation to their samples, and how are these rights safeguarded in your biobank?"
+ a="Patients have the right to revoke their consent at any time, which can be done at the clinic or biobank. The trustee, acting as an intermediary, will notify BOWL and DIZ to destroy the corresponding samples or data." />
+ </>
+ },
+ {
+ title: "",
+ vorname: "Nils",
+ nachnname: "Berelsmann",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "nberelsmann",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "",
+ nachnname: "Hammer",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "hammerkai",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "",
+ nachnname: "Ingatova",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "ignatova2",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "Muko",
+ nachnname: "Dino",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "dino",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "Marco",
+ nachnname: "Radukic",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "radukic",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "",
+ nachnname: "Psychologinnen",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "psychol",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+ {
+ title: "",
+ vorname: "",
+ nachnname: "Saito",
+ job: "",
+ affiliation: "",
+ pictureurl: pics['placeholder'],
+ tag: "Academia",
+ heading: "",
+ interviewtabid: "saito",
+ cardtext: "",
+ quote: "",
+ aimofcontact: "",
+ insights: "",
+ implementation: "",
+ summary: ""
+ },
+
]
diff --git a/src/data/steckbriefe.ts b/src/data/steckbriefe.ts
index b82f3076429478f582330e2ce8fdf9aeeecc0a4f..429d16c66f0b8f43813022ef5ce5e0fd7cf74d7d 100644
--- a/src/data/steckbriefe.ts
+++ b/src/data/steckbriefe.ts
@@ -221,7 +221,7 @@ export const teammembers: Array<SteckbriefInterface> = [
igemjob: ["Wet lab", "Delivery", "Creativity"],
whyigem: [
"It's great to be part of a project from the formation of the idea until the final results, so you can contribute with your work but also gain new experiences.",
- "Because I want to be part of a dedicated team of young scientists and follow a project from the idea to the final result with all its' challenges.",
+ "Because I want to be part of a dedicated team of young scientists and follow a project from the idea to the final result with all it's challenges.",
],
bestpart: [
"Learning new techniques in the lab",
diff --git a/src/data/stroke.svg b/src/data/stroke.svg
deleted file mode 100644
index 34ac0e5bfa474a681616a0565443f32157024b7b..0000000000000000000000000000000000000000
--- a/src/data/stroke.svg
+++ /dev/null
@@ -1,11 +0,0 @@
-<svg width="100" height="64" fill="none" xmlns="http://www.w3.org/2000/svg">
-<g clip-path="url(#a)">
-<path d="M-17 30.5C-1 22 72-4 54 13 37.9 28.2-2.5 57.5 16 55.5s72-29 104-40" stroke="#850F78" stroke-width="10"/>
-</g>
-<defs>
-<clipPath id="a">
-<path fill="#fff" d="M0 0h100v64H0z"/>
-</clipPath>
-</defs>
-</svg>
-
diff --git a/src/data/test-path-home.svg b/src/data/test-path-home.svg
deleted file mode 100644
index e095d6ad86b0f5629fc0e381a6f5de3fa409620b..0000000000000000000000000000000000000000
--- a/src/data/test-path-home.svg
+++ /dev/null
@@ -1,6 +0,0 @@
-
-<svg width="1080" height="4000" fill="none" xmlns="test-namespace">
-<path d="M 50 50 C 500 -50 1000 100 1870 50 C 1820 220 2024 528 1870 590 C 1351 678 118 451 54 561 C 3 672 12 985 55 985 C 586 1090 1342 898 1881 1038 C 1994 1194 1986 1568 1890 1681 C 1751 1803 281 1481 168 1646 C 81 1794 21 1977 168 2142 C 499 2246 1403 2325 1081 2142
-" stroke="#850F78" stroke-width="10"/>
-</svg>
-
diff --git a/src/data/timelinepersontabs.tsx b/src/data/timelinepersontabs.tsx
deleted file mode 100644
index a76f15ba8b9dbc41cc1fc8098cbe3c5a8f6cd6d9..0000000000000000000000000000000000000000
--- a/src/data/timelinepersontabs.tsx
+++ /dev/null
@@ -1,10 +0,0 @@
-
-
-
-
-export const timelinepersontabs = [
-
-
-
- ]
-
\ No newline at end of file
diff --git a/src/pages.ts b/src/pages.ts
index 62163b502eadf3c6bedf02998444c61ba7fb3162..822450206c20259377fce911d735734598714163 100644
--- a/src/pages.ts
+++ b/src/pages.ts
@@ -27,6 +27,7 @@ import { Methods } from "./contents/methods";
import { METHH } from "./headers/meth-h";
import { ConSidebar } from "./sidebars/conS";
import { iGemBielefeldSidebar } from "./sidebars/igbS";
+import { MethSidebar } from "./sidebars/methS";
import { PartSidebar } from "./sidebars/prtS";
import { ResultSidebar } from "./sidebars/resS";
@@ -162,7 +163,7 @@ const Pages: (Page | Folder)[] = [
path: "/materials-methods",
component: Methods,
header: METHH,
- navlist: NoSidebar,
+ navlist: MethSidebar,
},
{
name: "Notebook",
@@ -338,7 +339,7 @@ export const NavPages: (Page | PageRef | Folder)[] = [
path: "/materials-methods",
component: Methods,
header: METHH,
- navlist: NoSidebar,
+ navlist: MethSidebar,
},
{
name: "Results",
@@ -385,12 +386,12 @@ export const NavPages: (Page | PageRef | Folder)[] = [
path: "/human-practices?scrollTo=Integrated Human Practices3"
},
{
- name: "Public Engagement",
+ name: "Education",
title: "Education and Outreach",
path: "/human-practices?scrollTo=Further Engagement1H"
},
{
- name: "Education",
+ name: "Public Engagement",
title: "Education and Outreach",
path: "/human-practices?scrollTo=Further Engagement2H"
},
diff --git a/src/sidebars/descS.tsx b/src/sidebars/descS.tsx
index 01de44139f1a77af321b0726cf32dff917cbe55e..092edd995fa69bf782cddbdce4819e83394570fd 100644
--- a/src/sidebars/descS.tsx
+++ b/src/sidebars/descS.tsx
@@ -13,7 +13,7 @@ export function DescSidebar(){
const tabs = [
{ tab: "Abstract" },
{tab: "Our Motivation"},
- { tab: "Cystic Fibrosis", subtabs: ["Overview", "The CFTR Protein", "ΔF508", "Symptoms", "Diagnosis", "Treatment"]},
+ { tab: "Cystic Fibrosis", subtabs: ["Overview", "The CFTR Protein", "F508del", "Symptoms", "Diagnosis", "Treatment"]},
{tab: "Approach", subtabs: ["Mechanism", "Delivery"]},
{tab: "Our Vision"},
{tab: "References"}
diff --git a/src/sidebars/hpS.tsx b/src/sidebars/hpS.tsx
index 2bbbae28f92fa4f228a0d86790230a73843c160f..cb1e65bf7d87453373c3d32add9237cf9c41687a 100644
--- a/src/sidebars/hpS.tsx
+++ b/src/sidebars/hpS.tsx
@@ -16,7 +16,7 @@ const tabs = [
{ tab: "Overview" },
{tab: "Introduction"},
{tab: "Integrated Human Practices", subtabs: ["Framework", "Timeline", "Implementation", "Feedback", "Conclusion"]},
- {tab: "Further Engagement", subtabs: ["Public Engagement", "Education", "Entrepreneurship", "Collaborations", "Partnerships"]},
+ {tab: "Further Engagement", subtabs: [ "Education", "Public Engagement", "Entrepreneurship", "Collaborations", "Partnerships"]},
{tab: "Supplementary Material"},
// {tab: ""},
];
\ No newline at end of file
diff --git a/src/sidebars/igbS.tsx b/src/sidebars/igbS.tsx
index 8cb7469f76db1bba034f174291563a2582ed7a77..37af2cc32f0fecbda29b864882d1e81c18f6f807 100644
--- a/src/sidebars/igbS.tsx
+++ b/src/sidebars/igbS.tsx
@@ -12,7 +12,8 @@ export function iGemBielefeldSidebar(){
}
const tabs = [
- { tab: "History", subtabs: ["Origins", "Former Teams"]},
+ {tab: "Bielefeld University"},
+ { tab: "History"},
{ tab: "Steering Committee", subtabs: ["Function", "Jörn"]},
{tab: "Future"}
];
\ No newline at end of file
diff --git a/src/sidebars/methS.tsx b/src/sidebars/methS.tsx
new file mode 100644
index 0000000000000000000000000000000000000000..abc5b60e74fed383d426c04b4c0b52616e575c0d
--- /dev/null
+++ b/src/sidebars/methS.tsx
@@ -0,0 +1,17 @@
+import { createSidebar } from "../utils/createSidebar";
+
+export function MethSidebar(){
+ let sidebar = createSidebar(tabs);
+ return(
+ <div className="col-2 d-lg-block">
+ {sidebar}
+ </div>
+ )
+}
+
+
+const tabs = [
+ { tab: "Introduction"},
+ { tab: "Patch Clamp"},
+ {tab: "Cell Lines"},
+ ];
diff --git a/src/sidebars/none.tsx b/src/sidebars/none.tsx
index daff81f8e9a9fddaec1009c672b5c117c3a81796..5d9a2e76b4d7a5b3bd17cdae68f41df2e742eac9 100644
--- a/src/sidebars/none.tsx
+++ b/src/sidebars/none.tsx
@@ -1,6 +1,6 @@
export function NoSidebar(){
return(
- <div className="col-1 d-lg-block">
+ <div className="col-2 d-lg-block">
</div>
)
}
\ No newline at end of file