Prof. Dr. Kristian Müller emphasized the critical role of delivery systems in the success of gene therapies, particularly in the context of CF treatment. Two primary delivery mechanisms were discussed: AAVs (Adeno-associated viruses) and LNPs (Lipid nanoparticles), each with distinct advantages and limitations.
AAVs are a well-established vehicle in gene therapy, having been used successfully in various approved treatments. They are highly efficient at delivering genetic material to target cells, especially in well-characterized diseases like CF. One of their key strengths is their ability to precisely target specific tissues, making them particularly valuable for lung delivery in Cystic Fibrosis. However, AAVs come with notable challenges, primarily their limited packaging capacity (approximately 4.5 kilobases), which constrains the size of the genetic payload they can carry. Additionally, AAVs can elicit immune responses, particularly when multiple doses are required, posing a barrier to their long-term use.
On the other hand, LNPs offer a scalable and re-dosable alternative. LNPs have the advantage of a larger packaging capacity, allowing them to carry more complex genetic instructions or larger gene-editing tools, such as prime editors. They are also easier and cheaper to produce on a large scale, making them an attractive option for widespread clinical applications. A significant benefit of LNPs is their lower immunogenicity, which reduces the risk of adverse immune reactions upon repeated dosing. However, LNPs currently face challenges in specific targeting compared to AAVs. AAVs have a higher precision in targeting specific tissues, while LNPs still need optimization for targeted delivery to areas like the lungs.</p>],
implementation:[<p>Prof. Müller’s insights directly inform the implementation of our iGEM project, where we aim to design novel prime editors that are small enough to be delivered efficiently, while also exploring LNPs <OurLinkpath='engineering'tabId='delivery'scrollToId='del1head'text="exploring LNPs"/> as a scalable and re-dosable alternative to AAVs. By tailoring our approach to address the specific challenges of CF, such as mucus penetration and lung cell targeting, we can enhance the precision and efficacy of gene therapy. These innovations have the potential to set new standards in the field and contribute to broader research on genetic disease treatment.</p>],
implementation:[<p>Prof. Müller’s insights directly inform the implementation of our iGEM project, where we aim to design novel prime editors that are small enough to be delivered efficiently, while also <OurLinkpath='engineering'tabId="tab-delivery"scrollToId='del1head'text="exploring LNPs"/>{/*KAYA!*/}as a scalable and re-dosable alternative to AAVs. By tailoring our approach to address the specific challenges of CF, such as mucus penetration and lung cell targeting, we can enhance the precision and efficacy of gene therapy. These innovations have the potential to set new standards in the field and contribute to broader research on genetic disease treatment.</p>],
summary:[<p>In our interview with Prof. Dr. Kristian Müller, we explored the revolutionary potential of prime editing as a next-generation gene editing technology. Prof. Müller highlighted the advantages of prime editing over traditional CRISPR-Cas systems, particularly its ability to make precise genetic modifications without double-strand breaks, thus reducing off-target effects. He emphasized the importance of optimizing delivery systems, such as <OurLinkpath='engineering'tabId='delivery'scrollToId='del1head'text="AAV and LNPs"/>, and discussed the ethical considerations and biosafety measures crucial for advancing gene therapy. The interview underscored the significance of Cystic Fibrosis as a model disease, given its prevalence and the potential for impactful treatments through targeted genetic corrections.</p>],
months:"apr",
interview:<><iframetitle="Bielefeld-CeBiTec: Interview Müller AAV vs LNP (2024) [English]"width="560"height="315"src="https://video.igem.org/videos/embed/0613b6b8-7755-4373-9d86-9910fe30781f"frameBorder="0"allowFullScreen={true}sandbox="allow-same-origin allow-scripts allow-popups allow-forms"></iframe><p>This interview was recorded on video at a later date.</p></>,
quote:"It’s important to keep my hygiene practices practical and effective, focusing on regular cleaning rather than excessive measures that may create more risks for invection.",
summary:[<p>Inspired by <HPLinktoOtherHPTabtab="maxfirst"text="Max's"/> feedback on the unique challenges faced by individuals with immunocompromised systems, we initiated the development of a specialized <OurLinkpath='contribution'scrollToId='our-contributions'text="hygiene concept"/>. Max’s insights provided invaluable guidance in addressing the specific needs of cystic fibrosis (CF) patients and others with weakened immune systems. His input emphasized practical measures to ensure a safer and more hygienic environment in public spaces, particularly in university restrooms.
summary:[<p>Inspired by <HPLinktoOtherHPTabtab="maxfirst"text="Max's"/> feedback on the unique challenges faced by individuals with immunocompromised systems, we initiated the development of a specialized <OurLinkpath='contribution'scrollToId='hygiene-concept'text="hygiene concept"/>. Max’s insights provided invaluable guidance in addressing the specific needs of cystic fibrosis (CF) patients and others with weakened immune systems. His input emphasized practical measures to ensure a safer and more hygienic environment in public spaces, particularly in university restrooms.
Through detailed discussions with Max, we developed guidelines that balance rigorous hygiene with feasibility. His feedback highlighted that while regular cleaning and essential facilities like toilet lids are crucial, overly complex measures, such as contactless systems, may not be necessary if proper hand hygiene is maintained. He praised the initial points of the concept as thoughtful and effective, further refining our approach to focus on high-impact solutions.
To ensure a robust and comprehensive framework, we sought additional review and advice from <HPLinktoOtherHPTabtab="johannfunke"text="Johann Funke"/> . By incorporating Max’s feedback and Johann's expertise, we aim to create a practical hygiene protocol that addresses the needs of immunocompromised individuals, making university spaces safer and more inclusive. </p>],
We also learned that while new therapies are exciting, their success often depends on their practicality. Treatments that are complex, invasive, or burdensome are less likely to be adopted, even if they promise significant benefits. Simplicity, ease of use, and reducing the treatment burden are critical factors in ensuring patients fully engage with and benefit from these therapies.
These insights have shaped our approach, reinforcing the importance of considering both the psychological and practical aspects of new gene therapies, to better address the needs of CF patients and their families. </p>],
implementation:[<p>These findings directly influenced several key areas of the project. We adapted the project to emphasise ease of use and minimal disruption to patients' daily lives. For example, we focused on developing a therapy delivery system that was as non-invasive as possible. Recognising the mental health challenges, we integrated our project with a simple therapeutic method to reduce the mental burden on patients. We have emphasised transparency in communicating the benefits, risks and expectations of gene therapy to ensure that patients have a realistic understanding of the potential outcomes. This includes working closely with patient organisations to disseminate clear and accurate information. We are actively engaging with CF patient communities and healthcare professionals to gather ongoing feedback and ensure that the project evolves based on real patient experiences and challenges.
Therefore we used <OurLinkpath='human-practices'scrollToId='implementation-feedback'text="our survey"/> to gather feedback from patients and their families.
Therefore we used <OurLinkpath='human-practices'scrollToId='collapsible1'text="our survey"/> to gather feedback from patients and their families.
By integrating these insights, we aim to create a gene therapy project that addresses not only the medical needs, but also the emotional and practical concerns of CF patients and their families. </p>],
summary:"Our project aims to address the psychological and medical challenges faced by Cystic Fibrosis (CF) patients and their families, particularly regarding gene therapies. We engaged with psychologists and gathered insights from patients and caregivers, revealing significant emotional strain and a mix of optimism and concern about new treatments. Key findings highlighted the importance of psychological support and the practicality of therapies in ensuring patient engagement. In response, we are developing a user-friendly therapy delivery system that minimizes disruption to daily life while emphasizing transparent communication about treatment risks and benefits. Our goal is to create a comprehensive gene therapy solution that meets the medical and emotional needs of CF patients.",
