From d165019ed7644b794385873434d8462d3b301738 Mon Sep 17 00:00:00 2001
From: Kaya <kaya.lange@uni-bielefeld.de>
Date: Tue, 3 Dec 2024 23:27:03 +0100
Subject: [PATCH] hp nicole
---
src/data/hptimelinedata.tsx | 41 ++++++++++++++++++++-----------------
1 file changed, 22 insertions(+), 19 deletions(-)
diff --git a/src/data/hptimelinedata.tsx b/src/data/hptimelinedata.tsx
index 75c98e1..226c248 100644
--- a/src/data/hptimelinedata.tsx
+++ b/src/data/hptimelinedata.tsx
@@ -418,8 +418,7 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<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>],
+ </ul></p>],
summary: "The interview provided key insights into targeting ionocytes for CFTR-mRNA delivery, overcoming mucus barriers, and testing delivery effectiveness using Ussing chambers, organoids, and patch clamping, while also suggesting chitosan-based nanoparticles as a safer alternative to PEG-lipid systems.",
months: "may"
},
@@ -639,8 +638,8 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
quoteVorname: "Malte",
quote: "The interview proved to be invaluable in gaining an initial understanding of the principles of pegRNA design and optimization, 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 at the Boston Childrens Hospital. 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 change 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 reverse transcriptase template (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, optimize 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. ",
+ 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 change 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 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 reverse transcriptase template (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, optimize PBS selection and improve our overall approach to primer editing, especially in terms of the pegRNA design.",
+ implementation: [<p>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 PBS and RTTs, we adjusted the <OurLink path='engineering'tabId='pegrna' scrollToId="peg1head" text="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.</p>],
summary: "We engaged in a valuable discussion with Jan-Phillip Gerhards regarding prime editing and pegRNAs, leveraging his internship experience with these technologies. Key insights included the effectiveness of silent edits, which can enhance the safety of our PrimeGuide by modifying DNA sequences without altering the resultant protein, thereby preventing pegRNA rebinding. We also learned the importance of optimizing the primer binding site (PBS) length to achieve ideal temperatures close to 37°C, recommending lengths of 16-17 nucleotides. Additionally, we discovered the potential benefits of using non-annotated regions with overhangs for cloning, while also recognizing concerns about circRNA steric hindrance by Cas9. These insights directly informed our project, allowing us to refine our pegRNA design and cloning strategies, ultimately enhancing the precision and efficiency of our gene editing approach.",
months: "May"
},
@@ -884,17 +883,21 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<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="The approval process is distinct from the question of reimbursement by public health insurance and is not part of the AMNOG process. In Germany, CF is considered a rare disease if it affects fewer than five out of 10,000 people, and treatments for such rare diseases often face unique reimbursement challenges. If the prevalence exceeds this threshold, the disease is categorized as relatively common. In such cases, the AMNOG process evaluates the additional benefit (Zusatznutzen) of the treatment after it has already been approved, determining whether and to what extent costs will be reimbursed by statutory health insurance. This separation between approval and reimbursement highlights the different procedural and regulatory considerations for rare versus more common diseases.Have you heard about issues with reimbursement from private insurance companies?"/>
+ <QaBox q="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."
+ a="Why did your colleague have issues with private insurance?"/>
+ <QaBox q="He was privately insured, but the treatment was very expensive, around €16,000 per month, and the insurance company was reluctant to cover it."
+ a="Do you need legal information for your project?"/>
+ <QaBox q="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. 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="Do private and public insurance differ in covering gene therapies? "
+ a="Private insurance can sometimes be more flexible, but it varies case by case. In the example we discussed, the individual had to fight for coverage, even though private insurance is often seen as more lenient. Statutory insurance tends to have clearer guidelines but can also be restrictive. "/>
+ <QaBox q="What happens when someone with Cystic Fibrosis has an atypical form of the disease?"
+ a="Atypical cases can present significant challenges, particularly when test results don't align with standard expectations. For example, in cases like the one we encountered, a patient diagnosed with cystic fibrosis (CF) no longer met the clinical criteria for treatment reimbursement after a negative sweat test. Despite still having the disease, the medical indication for CF treatment was considered absent, leading to the partial or complete withdrawal of therapy coverage by the statutory health insurance (GKV). This highlights critical gaps in how the healthcare system addresses such cases, where rigid adherence to clinical guidelines may fail to accommodate the complexities of individual medical needs."/>
+ <QaBox q="Is there a mechanism within the health insurance system for dealing with atypical cases"
+ a="Yes, but it can be tricky. The statutory insurance system works based on established guidelines, so when someone doesn't fit those guidelines, they may struggle to receive coverage. There are no clear pathways for addressing atypical cases, which highlights the need for greater awareness in the medical community about these variations. "/>
<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?"
@@ -906,13 +909,13 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<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." />
+ 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. Is gene therapy research driven more by biology or medicine?" />
+ <QaBox q="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."
+ a="Do biologists or medical professionals develop gene therapies?" />
+ <QaBox q="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."
+ a="Does research in genome medicine and gene therapies come from biology, medicine, or both?" />
+ <QaBox q="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."
+ a="Thank you for asking me for an interview and also for answering my own questions so well"/>
</>,
summary: "Our discussion addressed the complexities of Cystic Fibrosis (CF) treatments, focusing on gene therapy and health insurance processes. We learned about the regulatory challenges gene therapies face, particularly regarding the European Medicines Agency (EMA) and the AMNOG process for reimbursement assessments. Public insurers impose stricter guidelines than private insurers, emphasizing the importance of early intervention in CF and the need for adaptable policies for atypical cases. We recognized the high costs associated with gene therapies and incorporated cost-benefit analysis into our project planning. Following the interview, we refined our approach to include straightforward delivery methods and attended a GxP course for regulatory compliance. Engaging with start-ups further informed our practical implementation strategies, ensuring our project aligns with both scientific and regulatory needs.",
months: "jun",
--
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