@@ -52,13 +52,13 @@ 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. 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<SupScrollLinklabel="3"/>{/* ehem6 */}. 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>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<SupScrollLinklabel="3"/>{/* ehem6 */}. 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>
<pdata-aos="zoom-y-out">Cystic Fibrosis (CF) is a common life-limiting genetic disorder, particularly affecting the Caucasian population, with approximately <b>162,400 people worldwide</b> living with the condition<SupScrollLinklabel="7"/>. Statistically, about <b>one in every 3,300</b> white newborns is born with CF <SupScrollLinklabel="8"/> . And according to the German Cystic Fibrosis Registry, the average life expectancy for children born with CF in 2021 was around 57 years <SupScrollLinklabel="9"/> , highlighting the severe and life-shortening nature of the disease. </p>
<p>The modern understanding of CF dates back to 1922 when Dr. Dorothy Andersen, a pediatric specialist, first described the disease and coined the term "Cystic Fibrosis"<SupScrollLinklabel="10"/>. In Germany, it is commonly known as "Mukoviszidose," derived from the Latin words meaning "mucus" and "viscous" <SupScrollLinklabel="10"/> , emphasizing the characteristic thick, sticky mucus that defines the condition <SupScrollLinklabel="11"/><sup>,</sup><SupScrollLinklabel="12"/>. </p>
<pdata-aos="zoom-y-out">Cystic Fibrosis (CF) is a common life-limiting genetic disorder, particularly affecting the Caucasian population, with approximately <b>162,400 people worldwide</b> living with the condition<SupScrollLinklabel="4"/>{/* ehem7 */}. Statistically, about <b>one in every 3,300</b> white newborns is born with CF <SupScrollLinklabel="8"/> . And according to the German Cystic Fibrosis Registry, the average life expectancy for children born with CF in 2021 was around 57 years <SupScrollLinklabel="9"/> , highlighting the severe and life-shortening nature of the disease. </p>
<p>The modern understanding of CF dates back to 1922 when Dr. Dorothy Andersen, a pediatric specialist, first described the disease and coined the term "Cystic Fibrosis"<SupScrollLinklabel="10"/>. In Germany, it is commonly known as "Mukoviszidose," derived from the Latin words meaning "mucus" and "viscous" <SupScrollLinklabel="10"/> , emphasizing the characteristic thick, sticky mucus that defines the condition <SupScrollLinklabel="11"/><sup>,</sup><SupScrollLinklabel="12"/>. </p>
<p>Genetic research has identified over 1,700 mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, with the F508del mutation being the most common, affecting about 70% of CF patients. This mutation prevents the proper folding of the CFTR protein, significantly impairing its function <SupScrollLinklabel="13"/> . </p>
<p>The CFTR protein regulates the flow of chloride ions across the membranes of cells in the lungs, digestive system, and other organs. This ion flow is essential for drawing water into surrounding tissues, which helps maintain the proper hydration and consistency of mucus. In patients with CF, the disruption of this process prevents sufficient water from entering the mucus, making it abnormally thick and sticky. The accumulation of this mucus leads to an obstruction of airways and digestive ducts, resulting in chronic lung infections, inflammation, impaired digestion, and malnutrition<SupScrollLinklabel="14"/> . </p>
<OneFigure
...
...
@@ -313,7 +313,7 @@ export function Description() {
</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. </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 <SupScrollLinklabel="3"/>{/* ehem6 */} . Additionally, LNPs can be engineered with targeting ligands or antibodies to precisely direct their payload to specific cell types, further enhancing their therapeutic efficacy <SupScrollLinklabel="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 <SupScrollLinklabel="8"/> . This versatility in design is essential for optimizing the delivery and effectiveness of LNP-based therapies.</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 <SupScrollLinklabel="3"/>{/* ehem6 */} . Additionally, LNPs can be engineered with targeting ligands or antibodies to precisely direct their payload to specific cell types, further enhancing their therapeutic efficacy <SupScrollLinklabel="4"/>{/* ehem7 */}. 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 <SupScrollLinklabel="8"/> . This versatility in design is essential for optimizing the delivery and effectiveness of LNP-based therapies.</p>
</Collapsible>
<Collapsibleid="Col2"open={false}title="Challenges of working with LNPs">
<p>Maintaining the stability of LNPs throughout formulation, storage, and delivery is critical, as factors like temperature changes, pH shifts, or mechanical stress can affect their integrity <SupScrollLinklabel="1"/><SupScrollLinklabel="2"/> . Equally important is ensuring efficient encapsulation of the genetic material, as any inefficiency can lead to degradation of the therapeutic cargo or inadequate delivery to the target cells. Once inside the body, LNPs face the challenge of cellular uptake and successful endosomal escape. If they cannot escape the endosome after entering the cells, there is a risk that the genetic material will be degraded in the lysosomes, limiting the efficacy of the treatment. In addition, the formulation must minimize immunogenicity and toxicity, particularly with repeated dosing, which is often necessary for chronic diseases <SupScrollLinklabel="2"/>. Achieving this sensitive balance is crucial for maximizing the therapeutic potential of LNPs in gene delivery.</p>
