From a23fc04649b7b96ec9aba9de2d4c2b990e98247c Mon Sep 17 00:00:00 2001 From: liliana <liliana.sanfilippo@uni-bielefeld.de> Date: Thu, 22 Aug 2024 15:42:53 +0200 Subject: [PATCH] project decription and citations --- code/bibtex.bib | 2 +- code/cit.py | 22 ++-- code/output.txt | 197 +++++++++++++++++------------------ src/App/App.css | 3 +- src/contents/description.tsx | 182 ++++++++++++++++++++++++-------- 5 files changed, 252 insertions(+), 154 deletions(-) diff --git a/code/bibtex.bib b/code/bibtex.bib index ef1ac06e..62500de8 100644 --- a/code/bibtex.bib +++ b/code/bibtex.bib @@ -18,6 +18,6 @@ author={Anzalone, Andrew V. and Randolph, Peyton B. and Davis, Jessie R. and Sou @article{Nelson_Randolph_Shen_Everette_Chen_Anzalone_An_Newby_Chen_Hsu_et al._2022, title={Engineered pegRNAs improve prime editing efficiency}, volume={40}, rights={2021 The Author(s), under exclusive licence to Springer Nature America, Inc.}, ISSN={1546-1696}, DOI={10.1038/s41587-021-01039-7}, abstractNote={Prime editing enables the installation of virtually any combination of point mutations, small insertions or small deletions in the DNA of living cells. A prime editing guide RNA (pegRNA) directs the prime editor protein to the targeted locus and also encodes the desired edit. Here we show that degradation of the 3′ region of the pegRNA that contains the reverse transcriptase template and the primer binding site can poison the activity of prime editing systems, impeding editing efficiency. We incorporated structured RNA motifs to the 3′ terminus of pegRNAs that enhance their stability and prevent degradation of the 3′ extension. The resulting engineered pegRNAs (epegRNAs) improve prime editing efficiency 3–4-fold in HeLa, U2OS and K562 cells and in primary human fibroblasts without increasing off-target editing activity. We optimized the choice of 3′ structural motif and developed pegLIT, a computational tool to identify non-interfering nucleotide linkers between pegRNAs and 3′ motifs. Finally, we showed that epegRNAs enhance the efficiency of the installation or correction of disease-relevant mutations.}, number={3}, journal={Nature Biotechnology}, publisher={Nature Publishing Group}, author={Nelson, James W. and Randolph, Peyton B. and Shen, Simon P. and Everette, Kelcee A. and Chen, Peter J. and Anzalone, Andrew V. and An, Meirui and Newby, Gregory A. and Chen, Jonathan C. and Hsu, Alvin and Liu, David R.}, year={2022}, month=mar, pages={402–410}, language={en} } - @article{Sousa_Hemez_Lei_Traore_Kulhankova_Newby_Doman_Oye_Pandey_Karp_et al._2024, title={Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells}, rights={2024 The Author(s)}, ISSN={2157-846X}, DOI={10.1038/s41551-024-01233-3}, abstractNote={Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE—engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal ‘dead’ single-guide RNAs—we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.}, journal={Nature Biomedical Engineering}, publisher={Nature Publishing Group}, author={Sousa, Alexander A. and Hemez, Colin and Lei, Lei and Traore, Soumba and Kulhankova, Katarina and Newby, Gregory A. and Doman, Jordan L. and Oye, Keyede and Pandey, Smriti and Karp, Philip H. and McCray, Paul B. and Liu, David R.}, year={2024}, month=jul, pages={1–15}, language={en} } + @article{Sousa_Hemez_Lei_Traore_Kulhankova_Newby_Doman_Oye_Pandey_Karp_et al._2024, title={Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells}, rights={2024 The Author(s)}, ISSN={2157-846X}, DOI={10.1038/s41551-024-01233-3}, abstractNote={Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE—engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal ‘dead’ single-guide RNAs—we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.}, journal={Nature Biomedical Engineering}, publisher={Nature Publishing Group}, volume={}, author={Sousa, Alexander A. and Hemez, Colin and Lei, Lei and Traore, Soumba and Kulhankova, Katarina and Newby, Gregory A. and Doman, Jordan L. and Oye, Keyede and Pandey, Smriti and Karp, Philip H. and McCray, Paul B. and Liu, David R.}, year={2024}, month=jul, pages={1–15}, language={en} } \ No newline at end of file diff --git a/code/cit.py b/code/cit.py index 4d1b377b..fbb57405 100644 --- a/code/cit.py +++ b/code/cit.py @@ -69,8 +69,8 @@ def main(): def articleHTML(dictio, x, out): print("Writing html code for entry "+ str(x+1) + "...") - out.write("#<!-- Citation num " + str(x+1) + "-->" + "\n") - out.write("<li typeof=\"schema:ScolarlyArticle\" role=\"doc-biblioentry\" property=\"schema:citation\" id=\"desc-" + str(x+1) + "\">"+ "\n") + out.write("{/*<!-- Citation num " + str(x+9) + "--> */}" + "\n") + out.write("<li typeof=\"schema:ScolarlyArticle\" role=\"doc-biblioentry\" property=\"schema:citation\" id=\"desc-" + str(x+9) + "\">"+ "\n") out.write("\t" + "<span property=\"schema:author\" typeof=\"schema:Person\">"+ "\n") print("Just a sec, seperating authors...") @@ -106,15 +106,15 @@ def articleHTML(dictio, x, out): name = last + ", " + first if a == liste[-1]: - out.write("\t" + "\t" +"<span property=\"schema:Name\">" +name + "</span>"+ "\n") + out.write("\t" + "\t" +"<span property=\"schema:Name\"> " +name + "</span>"+ "\n") else: - out.write("\t" +"\t" +"<span property=\"schema:Name\">" +name + "</span>,"+ "\n") + out.write("\t" +"\t" +"<span property=\"schema:Name\"> " +name + "</span>;"+ "\n") except Exception as e: print(f"An unexpected error occurred: {e} see " + a) out.write("\t" +"</span>"+ "\n") - out.write("\t" + "<span property=\"schema:name\">"+dictio['title']+ ".</span>"+ "\n") - out.write("\t" +"<i property=\"schema:publisher\" typeof=\"schema:Organization\">"+ dictio['journal'] +"</i>"+ "\n") - out.write("\t" +"<b property=\"issueNumber\" typeof=\"PublicationIssue\">"+dictio['volume']+"</b>,"+ "\n") + out.write("\t" + "<span property=\"schema:name\"> "+dictio['title']+ ". </span>"+ "\n") + out.write("\t" +"<i property=\"schema:publisher\" typeof=\"schema:Organization\"> "+ dictio['journal'] +"</i>"+ "\n") + out.write("\t" +"<b property=\"issueNumber\" typeof=\"PublicationIssue\"> "+dictio['volume']+"</b>, "+ "\n") print("Getting pages...") try: pages = dictio['pages'] @@ -124,12 +124,12 @@ def articleHTML(dictio, x, out): pag = pages.split("--") begin = pag[0].strip() end = pag[1].strip() - out.write("\t" + "<span property=\"schema:pageBegin\">"+ begin +"</span>-<span property=\"schema:pageEnd\">"+ end + "</span>"+ "\n") + out.write("\t" + "<span property=\"schema:pageBegin\"> "+ begin +"</span>-<span property=\"schema:pageEnd\">"+ end + "</span>"+ "\n") elif '-' in pages: pag = pages.split("-") begin = pag[0].strip() end = pag[1].strip() - out.write("\t" + "<span property=\"schema:pageBegin\">"+ begin +"</span>-<span property=\"schema:pageEnd\">"+ end + "</span>"+ "\n") + out.write("\t" + "<span property=\"schema:pageBegin\"> "+ begin +"</span>-<span property=\"schema:pageEnd\">"+ end + "</span>"+ "\n") elif len(pages) > 0: out.write("\t" + "<span property=\"schema:pageBegin\">"+ pages +"</span>"+ "\n") else: @@ -146,11 +146,11 @@ def articleHTML(dictio, x, out): problemlist.append("Check for missing page info at " + str (x+1)) year = dictio['year'] - out.write("\t" +"(<time property=\"schema:datePublished\" datatype=\"xsd:gYear\" datetime=\"" + year + "\">"+year+"</time>)."+ "\n") + out.write("\t" +"(<time property=\"schema:datePublished\" datatype=\"xsd:gYear\" dateTime=\" " + year + "\">"+year+"</time>)."+ "\n") try: doi = dictio['doi'] - out.write("\t" +"<a class=\"doi\" href=\"https://doi.org/"+doi+"\">doi: "+doi+"</a>"+ "\n") + out.write("\t" +"<a className=\"doi\" href=\"https://doi.org/"+doi+"\"> doi: "+doi+"</a>"+ "\n") except KeyError as e: print("Sorry, no doi information") problemlist.append("Check for missing doi info at " + str (x+1)) diff --git a/code/output.txt b/code/output.txt index d9f12546..b5e64c92 100644 --- a/code/output.txt +++ b/code/output.txt @@ -1,120 +1,117 @@ -#<!-- Citation num 1--> -<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-1"> +{/*<!-- 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">Scotet, V.</span>, - <span property="schema:Name">Gutierrez, H.</span>, - <span property="schema:Name">Farrell, P.</span> + <span property="schema:Name"> Anzalone, A.</span>; + <span property="schema:Name"> Randolph, P.</span>; + <span property="schema:Name"> Davis, J.</span>; + <span property="schema:Name"> Sousa, A.</span>; + <span property="schema:Name"> Koblan, L.</span>; + <span property="schema:Name"> Levy, J.</span>; + <span property="schema:Name"> Chen, P.</span>; + <span property="schema:Name"> Wilson, C.</span>; + <span property="schema:Name"> Newby, G.</span>; + <span property="schema:Name"> Raguram, A.</span>; + <span property="schema:Name"> Liu, D.</span> </span> - <span property="schema:name">Newborn Screening for CF across the Globe—Where Is It Worthwhile?.</span> - <i property="schema:publisher" typeof="schema:Organization">Int J Neonatal Screen</i> - <b property="issueNumber" typeof="PublicationIssue">6</b>, - <span property="schema:pageBegin">18</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2020">2020</time>). - <a class="doi" href="https://doi.org/10.3390/ijn6010018">doi: 10.3390/ijn6010018</a> + <span property="schema:name"> Search-and-replace genome editing without double-strand breaks or donor DNA. </span> + <i property="schema:publisher" typeof="schema:Organization"> Nature</i> + <b property="issueNumber" typeof="PublicationIssue"> 576</b>, + <span property="schema:pageBegin">149–157</span> + (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2019">2019</time>). + <a className="doi" href="https://doi.org/10.1038/s41586-019-1711-4"> doi: 10.1038/s41586-019-1711-4</a> </li> -#<!-- Citation num 2--> -<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-2"> +{/*<!-- 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">Anzalone, A.V.</span>, - <span property="schema:Name">Randolph, P.B.</span>, - <span property="schema:Name">Davis, J.R.</span>, - <span property="schema:Name">Sousa, A.A.</span>, - <span property="schema:Name">Koblan, L.W.</span>, - <span property="schema:Name">Levy, J.M.</span>, - <span property="schema:Name">Newby, G.A.</span>, - <span property="schema:Name">Raguram, A.</span>, - <span property="schema:Name">Liu, D.R.</span> + <span property="schema:Name"> Doman, J.</span>; + <span property="schema:Name"> Pandey, S.</span>; + <span property="schema:Name"> Neugebauer, M.</span>; + <span property="schema:Name"> An, M.</span>; + <span property="schema:Name"> Davis, J.</span>; + <span property="schema:Name"> Randolph, P.</span>; + <span property="schema:Name"> McElroy, A.</span>; + <span property="schema:Name"> Gao, X.</span>; + <span property="schema:Name"> Raguram, A.</span>; + <span property="schema:Name"> Richter, M.</span>; + <span property="schema:Name"> Everette, K.</span>; + <span property="schema:Name"> Banskota, S.</span>; + <span property="schema:Name"> Tian, K.</span>; + <span property="schema:Name"> Tao, Y.</span>; + <span property="schema:Name"> Tolar, J.</span>; + <span property="schema:Name"> Osborn, M.</span>; + <span property="schema:Name"> Liu, D.</span> </span> - <span property="schema:name">Search-and-replace genome editing without double-strand breaks or donor DNA.</span> - <i property="schema:publisher" typeof="schema:Organization">Nature</i> - <b property="issueNumber" typeof="PublicationIssue">574</b>, - <span property="schema:pageBegin">589</span>-<span property="schema:pageEnd">594</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2019">2019</time>). - <a class="doi" href="https://doi.org/10.1038/s41586-019-1711-4">doi: 10.1038/s41586-019-1711-4</a> + <span property="schema:name"> Phage-assisted evolution and protein engineering yield compact, efficient prime editors. </span> + <i property="schema:publisher" typeof="schema:Organization"> Cell</i> + <b property="issueNumber" typeof="PublicationIssue"> 186</b>, + <span property="schema:pageBegin"> 3983</span>-<span property="schema:pageEnd">4002.e26</span> + (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2023">2023</time>). + <a className="doi" href="https://doi.org/10.1016/j.cell.2023.07.039"> doi: 10.1016/j.cell.2023.07.039</a> </li> -#<!-- Citation num 3--> -<li typeof="schema:WebPage" role="doc-biblioentry" property="schema:citation" id="desc-3"> - <span property="schema:author" typeof="schema:Organisation"> - <span property="schema:Name">Broad Institute of MIT and Harvard</span>. - </span> - <span property="schema:name">Researchers engineer in vivo delivery system for prime editing, partially restoring vision in mice.</span> - <i property="schema:publisher" typeof="schema:Organization">Phys.org</i> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2024">2024</time>). -</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">Gaudelli, N.</span>, - <span property="schema:Name">Komor, A.</span>, - <span property="schema:Name">Rees, H.</span>, - <span property="schema:Name">Packer, M.</span>, - <span property="schema:Name">Badran, A.</span>, - <span property="schema:Name">Bryson, D.</span>, - <span property="schema:Name">Liu, D.</span> - </span> - <span property="schema:name">Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage.</span> - <i property="schema:publisher" typeof="schema:Organization">Nature</i> - <b property="issueNumber" typeof="PublicationIssue">533</b>, - <span property="schema:pageBegin">420</span>-<span property="schema:pageEnd">424</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2016">2016</time>). - <a class="doi" href="https://doi.org/10.1038/nature17946">doi: 10.1038/nature17946</a> -</li> - -#<!-- Citation num 5--> -<li typeof="schema:WebPage" role="doc-biblioentry" property="schema:citation" id="desc-5"> - <span property="schema:author" typeof="schema:Organisation"> - <span property="schema:Name">OpenEd CUNY</span>. - </span> - <span property="schema:name">RNA Stability and the Role of RNA-Binding Proteins.</span> - <i property="schema:publisher" typeof="schema:Organization">OpenEd CUNY</i> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2024">2024</time>). -</li> - -#<!-- Citation num 6--> -<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-6"> +{/*<!-- Citation num 11--> */} +<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-11"> <span property="schema:author" typeof="schema:Person"> - <span property="schema:Name">Sahay, G.</span>, - <span property="schema:Name">Alakhova, D.Y.</span>, - <span property="schema:Name">Kabanov, A.V.</span> + <span property="schema:Name"> Jinek, M.</span>; + <span property="schema:Name"> Chylinski, K.</span>; + <span property="schema:Name"> Fonfara, I.</span>; + <span property="schema:Name"> Hauer, M.</span>; + <span property="schema:Name"> Doudna, J.</span>; + <span property="schema:Name"> Charpentier, E.</span> </span> - <span property="schema:name">Endocytosis of nanomedicines.</span> - <i property="schema:publisher" typeof="schema:Organization">Journal of Controlled Release</i> - <b property="issueNumber" typeof="PublicationIssue">145</b>, - <span property="schema:pageBegin">182</span>-<span property="schema:pageEnd">195</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2010">2010</time>). - <a class="doi" href="https://doi.org/10.1016/j.jconrel.2010.01.036">doi: 10.1016/j.jconrel.2010.01.036</a> + <span property="schema:name"> A programmable dual RNA-guided DNA endonuclease in adaptive bacterial immunity. </span> + <i property="schema:publisher" typeof="schema:Organization"> Science (New York, N.Y.)</i> + <b property="issueNumber" typeof="PublicationIssue"> 337</b>, + <span property="schema:pageBegin">816–821</span> + (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2012">2012</time>). + <a className="doi" href="https://doi.org/10.1126/science.1225829"> doi: 10.1126/science.1225829</a> </li> -#<!-- Citation num 7--> -<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-7"> +{/*<!-- 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">Ramachandran, S.</span>, - <span property="schema:Name">Satapathy, S.R.</span>, - <span property="schema:Name">Dutta, T.</span> + <span property="schema:Name"> Nelson, J.</span>; + <span property="schema:Name"> Randolph, P.</span>; + <span property="schema:Name"> Shen, S.</span>; + <span property="schema:Name"> Everette, K.</span>; + <span property="schema:Name"> Chen, P.</span>; + <span property="schema:Name"> Anzalone, A.</span>; + <span property="schema:Name"> An, M.</span>; + <span property="schema:Name"> Newby, G.</span>; + <span property="schema:Name"> Chen, J.</span>; + <span property="schema:Name"> Hsu, A.</span>; + <span property="schema:Name"> Liu, D.</span> </span> - <span property="schema:name">Delivery Strategies for mRNA Vaccines.</span> - <i property="schema:publisher" typeof="schema:Organization">Pharmaceutical Medicine</i> - <b property="issueNumber" typeof="PublicationIssue">36</b>, - <span property="schema:pageBegin">11</span>-<span property="schema:pageEnd">20</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2022">2022</time>). - <a class="doi" href="https://doi.org/10.1007/s40290-021-00417-5">doi: 10.1007/s40290-021-00417-5</a> + <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">402–410</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 8--> -<li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-8"> +{/*<!-- 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">Bandi, S.P.</span>, - <span property="schema:Name">Bhatnagar, S.</span>, - <span property="schema:Name">Venuganti, V.V.K.</span> + <span property="schema:Name"> Sousa, A.</span>; + <span property="schema:Name"> Hemez, C.</span>; + <span property="schema:Name"> Lei, L.</span>; + <span property="schema:Name"> Traore, S.</span>; + <span property="schema:Name"> Kulhankova, K.</span>; + <span property="schema:Name"> Newby, G.</span>; + <span property="schema:Name"> Doman, J.</span>; + <span property="schema:Name"> Oye, K.</span>; + <span property="schema:Name"> Pandey, S.</span>; + <span property="schema:Name"> Karp, P.</span>; + <span property="schema:Name"> McCray, P.</span>; + <span property="schema:Name"> Liu, D.</span> </span> - <span property="schema:name">Advanced materials for drug delivery across mucosal barriers.</span> - <i property="schema:publisher" typeof="schema:Organization">Acta Biomaterialia</i> - <b property="issueNumber" typeof="PublicationIssue">119</b>, - <span property="schema:pageBegin">13</span>-<span property="schema:pageEnd">29</span> - (<time property="schema:datePublished" datatype="xsd:gYear" datetime="2021">2021</time>). - <a class="doi" href="https://doi.org/10.1016/j.actbio.2020.10.031">doi: 10.1016/j.actbio.2020.10.031</a> + <span property="schema:name"> Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells. </span> + <i property="schema:publisher" typeof="schema:Organization"> Nature Biomedical Engineering</i> + <b property="issueNumber" typeof="PublicationIssue"> </b>, + <span property="schema:pageBegin">1–15</span> + (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2024">2024</time>). + <a className="doi" href="https://doi.org/10.1038/s41551-024-01233-3"> doi: 10.1038/s41551-024-01233-3</a> </li> diff --git a/src/App/App.css b/src/App/App.css index 12f1138e..14564710 100644 --- a/src/App/App.css +++ b/src/App/App.css @@ -951,8 +951,9 @@ svg{ /*collapsible*/ .collapse-card { + margin-bottom: 20px; border-radius: 4px; - margin-top: 10px; + margin-top: 20px; color: #333; padding: 5px; box-shadow: 0 4px 6px 0 hsla(0, 0%, 0%, 0.2); diff --git a/src/contents/description.tsx b/src/contents/description.tsx index 5d048de0..7c7e241b 100644 --- a/src/contents/description.tsx +++ b/src/contents/description.tsx @@ -1,7 +1,8 @@ import { InfoBox } from "../components/Boxes"; import { TabButtonRow } from "../components/Buttons"; -import Collapsible, { CollapsibleInfoBox } from "../components/Collapsible"; +import Collapsible from "../components/Collapsible"; import { H2} from "../components/headings"; +import { LoremMedium, LoremShort } from "../components/loremipsum"; import { Circle } from "../components/Shapes"; import { Complex } from "../components/svgs"; import { ButtonRowTabs } from "../components/Tabs"; @@ -21,18 +22,19 @@ export function Description() { <div className="col"> <section id="Cystic Fibrosis" className="section"> <H2 text="Cystic Fibrosis"/> - {/* <h3>General</h3> */} + <h3>General</h3> <div className="row align-items-center"> <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<a href="#desc-one"><sup>1</sup></a>.</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><LoremMedium/></p> </div> <div className="col-2 "> <Circle text="1:3000 newborns worldwide"/> <Circle text="x:y newborns in Germany"/> <Circle text="kosten"/> </div> - {/* <LineChart + {/* <Linear xAxis={[{ data: [1, 2, 3, 5, 8, 10] }]} series={[ { @@ -41,9 +43,9 @@ export function Description() { ]} width={500} height={300} - /> */} + /> */} </div> - {/* <div className="col"> + <div className="col"> <img src="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png"></img> </div> <h3>CFTR</h3> @@ -53,7 +55,7 @@ export function Description() { <img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/> </div> <div className="col"> - <p>Text about CFTR</p> + <p>Text about CFTR <LoremMedium/></p> </div> </div> <img src="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png"/> @@ -61,17 +63,18 @@ export function Description() { <p>Text about symptoms</p> <Collapsible title="How the symptoms affect different parts of the body" ></Collapsible> <h3>Diagnosis</h3> - <p>About the ways one can be diagnosed</p> + <p>About the ways one can be diagnosed <LoremMedium/></p> <div className="row align-items-center"> <div className="col" > <img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/> </div> <div className="col" > How newbornscreening affected the numbers. + <LoremMedium/> </div> - </div>*/} - {/* <h3>Treatment</h3> */} - {/*<img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/> */} + </div> + <h3>Treatment</h3> + <img src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/> <Collapsible title="Different types of drugs" > <TabButtonRow data={medibuttonrowdata} opentype="meditabs" closing=""/> <ButtonRowTabs data={medibuttonrowdata} cla="meditabs"/> @@ -87,7 +90,7 @@ export function Description() { <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> <div className="row align-items-center"> <div className="col" > - About del508 + About del508 <LoremMedium/> </div> <div className="col" > <img className="img" src="https://static.igem.wiki/teams/5247/placeholders/placehilderperson.jpeg"/> @@ -105,6 +108,7 @@ export function Description() { <details> <summary>Prime editing is a new method of gene editing based on an RNA-Protein complex. It was developed by a group of researchers revolving around Professor David Liu from Harvard University in 2019. <a href="#desc-nine"><sup>9</sup></a></summary> <p>Details</p> + <LoremMedium/> </details> </InfoBox> {/* <img className="img-right img-half" src="https://static.igem.wiki/teams/5247/scientific-figures/komplex-komplett-beschriftet.svg"/> @@ -114,11 +118,11 @@ export function Description() { <p>However, the Prime Editing complex is relatively large, posing challenges for therapeutic delivery<a href="#desc-three"><sup>3</sup></a>. Additionally, Prime Editing has been shown to be relatively inefficient in terms of gene editing rates, which could limit its therapeutic utility<a href="#desc-four"><sup>4</sup></a>. Our project aims to enhance the Prime Editing approach by miniaturizing its components. Fanzor, a recently discovered eukaryotic endonuclease, performs functions similar to Cas9, a crucial part of the Prime Editing complex, but is significantly smaller. We aim to substitute Cas9 with Fanzor. </p> <p>Additionally, we plan to replace the reverse transcriptase in the Prime Editing complex with a smaller RT variant. Furthermore, MCP proteins will be added to the Prime Editing complex to increase its stability<a href="#desc-five"><sup>5</sup></a>. </p> </div> - {/* <Collapsible title="Cas vs. Fanzor" ></Collapsible> */} + <Collapsible title="Cas vs. Fanzor" ></Collapsible> <p>The pegRNA is optimized via an extension by a stem loop, which stabilizes the RNA by protecting it from RNases and serves as a binding site for the MCP, which also supports the secondary RNA structure. Additionally, the pegRNA contains a riboswitch, a sodium ion-controlled regulator that switches off the complex. This represents a major biosafety feature in that the complex is switched off after successful DNA editing and the subsequent increased influx of chloride ions into the cell. The pegRNA is combined with an optimized sgRNA resulting in higher on-target effect. Overall, its optimization leads to a longer shelf life and an increase in the biosafety of the complex. </p> -{/* <InfoBox title="Riboswitch"> + <InfoBox title="Riboswitch"> About the Riboswitch - </InfoBox> */} + </InfoBox> </section> </div> @@ -130,12 +134,12 @@ export function Description() { <p>We chose LNPs as the delivery system of our Next-Generation Prime Editing Technology. Because of their large capacity and less immunogenic side effects compared to other delivery systems like Adeno-associated Viruses (AVV)<a href="#desc-six"><sup>6</sup></a>. Our aim is to optimize the LNP formulation to improve delivery to lung tissue via inhalation. Because of our collaborations, we are able to test and optimize different delivery systems to improve our organ specific therapeutic approach. Therefore, our LNP design focusses on stability and targeting. Stability is achieved by a polyethylene glycol (PEG) coating that protects the LNPs from degradation by the immune system<a href="#desc-seven"><sup>7</sup></a>. Moreover, we use capsaicin in combination with chitosan to improve the uptake of our construct through their mucus-adhesive properties<a href="#desc-eight"><sup>8</sup></a>. </p> </div> <div className="row align-items-center"> -{/* <div className="col"> - LAgertemperatur der Parts + <div className="col"> + LAgertemperatur der Parts <LoremShort/> </div> <div className="col"> - Trocknung - </div> */} + Trocknung <LoremShort/> + </div> </div> <p>We are furthermore optimising the LNPs for pulmonary therapy and investigating delivery by nebulisation as a non-invasive method compared to systemic approaches to make the therapy more convenient for patients. For specific targeting, we are focussing on marker proteins of basal cells and ionocytes that produce particularly high levels of CFTR protein and which we want to target with appropriate antibodies<a href="#desc-nine"><sup>9</sup></a>. Our workflow includes testing our next generation Prime Editing Technology delivered by our optimized LNPs in cell culture lines but also in primary nasal epithelial cells of CF patients to evaluate our optimizations and further improvements in vitro. We can also provide the outlook on the adaptation of the delivery system enabling systemic applications as well. </p> </section> @@ -146,7 +150,7 @@ export function Description() { <H2 text="Our vision"></H2> <p>We are envisioning a potential integration into a broader therapeutic framework involving customized gene editing tools for various genetic disorders, that present similar problems/difficulties to the F508del mutation, as well as other genetic diseases of different causes. This could include collaborations with pharmaceutical companies to develop new treatment modalities for genetic diseases beyond cystic fibrosis, utilizing advanced delivery systems and personalized medicine approaches. </p> - <H2 text="Editing Statistics"/> + {/* <H2 text="Editing Statistics"/> */} {/* <PieChart /> */} {/* Render the PieChart component */} </section> </div> @@ -274,28 +278,124 @@ export function Description() { (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2021">2021</time>). <a className="doi" href="https://doi.org/10.1016/j.actbio.2020.10.031"> doi: 10.1016/j.actbio.2020.10.031</a> </li> - {/* <!-- Citation num 9--> */} - <li typeof="schema:ScolarlyArticle" role="doc-biblioentry" property="schema:citation" id="desc-nine"> - <span property="schema:author" typeof="schema:Person"> - <span property="schema:Name">Anzalone, A.V.</span>, - <span property="schema:Name"> Randolph, P.B.</span>, - <span property="schema:Name"> Davis, J.R.</span>, - <span property="schema:Name"> Sousa, A.A.</span>, - <span property="schema:Name"> Koblan, L.W.</span>, - <span property="schema:Name"> Levy, J.M.</span>, - <span property="schema:Name"> Chen, P.J.</span>, - <span property="schema:Name"> Wilson, C.</span>, - <span property="schema:Name"> Newby, G.A.</span>, - <span property="schema:Name"> Raguram, A.</span>, - <span property="schema:Name"> Liu, D.R.</span> - </span> - <span property="schema:name"> Search-and-replace genome editing without double-strand breaks or donor DNA.</span> - <i property="schema:publisher" typeof="schema:Organization"> Nature </i> - <b property="issueNumber" typeof="PublicationIssue">7785</b>, - <span property="schema:pageBegin"> 149</span>-<span property="schema:pageEnd">157 </span> - (<time property="schema:datePublished" datatype="xsd:gYear" dateTime="2021">2019</time>). - <a className="doi" href="https://doi.org/10.1038/s41586-019-1711-4"> doi: 10.1038/s41586-019-1711-4</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"> Anzalone, A.</span>; + <span property="schema:Name"> Randolph, P.</span>; + <span property="schema:Name"> Davis, J.</span>; + <span property="schema:Name"> Sousa, A.</span>; + <span property="schema:Name"> Koblan, L.</span>; + <span property="schema:Name"> Levy, J.</span>; + <span property="schema:Name"> Chen, P.</span>; + <span property="schema:Name"> Wilson, C.</span>; + <span property="schema:Name"> Newby, G.</span>; + <span property="schema:Name"> Raguram, A.</span>; + <span property="schema:Name"> Liu, D.</span> + </span> + <span property="schema:name"> Search-and-replace genome editing without double-strand breaks or donor DNA. </span> + <i property="schema:publisher" typeof="schema:Organization"> Nature</i> + <b property="issueNumber" typeof="PublicationIssue"> 576</b>, + <span property="schema:pageBegin">149–157</span> + (<time property="schema:datePublished" datatype="xsd:gYear" dateTime=" 2019">2019</time>). + <a className="doi" href="https://doi.org/10.1038/s41586-019-1711-4"> doi: 10.1038/s41586-019-1711-4</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"> Doman, J.</span>; 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