diff --git a/src/contents/description.tsx b/src/contents/description.tsx index 1be83633de4dbd56fb80aee2256f15a9af964e1e..2ea02a4f7521790e79da800c3fefba33c0e082f4 100644 --- a/src/contents/description.tsx +++ b/src/contents/description.tsx @@ -51,7 +51,7 @@ export function Description() { /> </div> </div> - <p>By focusing on the F508del mutation, we also hope to contribute valuable insights to the global Cystic Fibrosis community. Although this mutation is most common in European populations, it is also found in other regions around the world<SupScrollLink label="5"/>. Our research could thus help inform treatment strategies and health policies on an international scale. </p> + <p>By focusing on the F508del mutation, we also hope to contribute valuable insights to the global Cystic Fibrosis community. Although this mutation is most common in European populations, it is also found in other regions around the world. Our research could thus help inform treatment strategies and health policies on an international scale. </p> <p>With several team members focusing their studies on biomedical fields, we began by examining the current landscape of CF treatments. It quickly became clear that, despite recent progress, there is still no cure. Most therapies, such as CFTR modulators, focus on managing symptoms and improving lung function rather than addressing the underlying cause of the disease <SupScrollLink label="6"/> . This realization led us to explore gene-editing technologies, thus leading us to Prime Editing—a next generation gene editing method—captured our attention. </p> <p>While Prime Editing holds great promise, we found that its application for Cystic Fibrosis, particularly the F508del mutation, had not been fully explored. Recognizing this gap in the research inspired us to take on the challenge of optimizing Prime Editing for this specific mutation. Our mission became clear: we want to contribute to the development of a potential therapeutic approach for Cystic Fibrosis, specifically targeting the F508del mutation with prime editing, and bring us closer to a long-term solution for patients. </p> </Section> @@ -312,7 +312,7 @@ export function Description() { <p>LNPs are pivotal not only for shielding mRNA but also for ensuring its efficient delivery into target cells. They facilitate cellular uptake through endocytosis, where the cell membrane engulfs the nanoparticle. LNPs are acclaimed for their high drug-loading capacities, which greatly enhance their therapeutic effectiveness. However, the success of this delivery hinges on effective endosomal escape. Ideally, LNPs release their mRNA payload into the cytoplasm after escaping from endosomes. If this escape process is inefficient, the mRNA can be degraded by lysosomes, which poses a significant challenge for mRNA vaccines and therapies.</p> </div> </div> - <p>A crucial advancement in LNP technology involves the use of pH-sensitive cationizable lipids. These lipids remain neutral at physiological pH but become cationic in the acidic environment of endosomes. This shift in charge helps dissociate the nanoparticles and disrupt the endosomal membrane, enhancing the likelihood of successful endosomal escape <SupScrollLink label="5"/> . </p> + <p>A crucial advancement in LNP technology involves the use of pH-sensitive cationizable lipids. These lipids remain neutral at physiological pH but become cationic in the acidic environment of endosomes. This shift in charge helps dissociate the nanoparticles and disrupt the endosomal membrane, enhancing the likelihood of successful endosomal escape. </p> <p>Moreover, the surface of LNPs can be customized to improve targeting. For instance, incorporating specific lipids or modifying the surface with charged groups can direct the delivery of mRNA to targeted organs like the lungs or spleen <SupScrollLink label="6"/> . Additionally, LNPs can be engineered with targeting ligands or antibodies to precisely direct their payload to specific cell types, further enhancing their therapeutic efficacy <SupScrollLink label="7"/> . Another approach can be chitosan-based nanoparticles have been explored for their ability to adhere to mucus and enhance drug delivery through the respiratory tract. These nanoparticles can penetrate through the mucus layer to reach the lung tissues more effectively <SupScrollLink label="8"/> . This versatility in design is essential for optimizing the delivery and effectiveness of LNP-based therapies.</p> </Collapsible> <Collapsible id="Col2" open={false} title="Challenges of working with LNPs"> @@ -320,9 +320,9 @@ export function Description() { <p>While these are general difficulties in the use of LNPs for gene therapy, further challenges arise when administering the LNPs via inhalation into the lungs, due to the unique environment and anatomy of the respiratory system.</p> <H4 text="Challenges of inhalated lung-specific LNPs" id="chall2" /> <p>These challenges range from formulation and particle size to overcoming biological barriers and maintaining consistent dosing, all of which impact the overall efficacy of the therapy. </p> - <p>When transforming LNP formulations into inhalable particles, even greater attention must be paid to stability than is already the case. During processes like nebulization or spray-drying, LNPs are exposed to strong <strong>mechanical stress</strong> such as shear forces during aerosolization that can damage the LNP and thus their ability to protect and deliver genetic material effectively <SupScrollLink label="5"/> . Ensuring that the LNPs maintain their structure throughout this transformation while remaining suitable for aerosol delivery is critical to the success of the therapy.</p> + <p>When transforming LNP formulations into inhalable particles, even greater attention must be paid to stability than is already the case. During processes like nebulization or spray-drying, LNPs are exposed to strong <strong>mechanical stress</strong> such as shear forces during aerosolization that can damage the LNP and thus their ability to protect and deliver genetic material effectively. Ensuring that the LNPs maintain their structure throughout this transformation while remaining suitable for aerosol delivery is critical to the success of the therapy.</p> <p>The <strong>size</strong> of the nanoparticles is another important factor. For successful lung delivery, LNPs should be smaller than 2 µm <SupScrollLink label="6"/> . If the particles are too large, there is a risk that they will get stuck in the upper airways not able to reach the target cells; if they are too small, they may be exhaled before reaching the deeper lung tissue. The right particle size is crucial for the LNPs to reach the alveoli, where they can provide the greatest therapeutic impact.</p> - <p>Another major challenge is overcoming the lungs' natural <strong>protective barriers</strong>. The airways are lined with mucus and surfactants, which help to defend against pathogens, but also make it difficult for LNPs to be transported. In diseases such as Cystic Fibrosis, the thickened mucus presents an even greater obstacle, making it more difficult for the LNPs to reach the target cells <SupScrollLink label="5"/> . The development of LNPs that can penetrate these barriers is essential for the success of gene therapy. </p> + <p>Another major challenge is overcoming the lungs' natural <strong>protective barriers</strong>. The airways are lined with mucus and surfactants, which help to defend against pathogens, but also make it difficult for LNPs to be transported. In diseases such as Cystic Fibrosis, the thickened mucus presents an even greater obstacle, making it more difficult for the LNPs to reach the target cells. The development of LNPs that can penetrate these barriers is essential for the success of gene therapy. </p> <p>Finally, inhaled administration leads to fluctuations in the consistency of the <strong>dosage</strong>. Unlike intravenous administration, where dosing can be strictly controlled, the results of inhalation are influenced by factors such as the patient's breathing pattern, lung capacity and inhalation technique. These variables can affect how much of the LNP formulation actually reaches the lungs, complicating efforts to maintain a consistent therapeutic dose over time, which is a reasonable price to pay when you consider that inhalation is a non-invasive form of therapy compared to systemic therapy via injections into the bloodstream</p> <p>All these challenges complicate the work with LNPs and present scientists with a great challenge, which makes working with LNPs even more important to find solutions.</p> </Collapsible>