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<p>Max</p>
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<Sectiontitle="Approach"id="Approach">
<Subesctiontitle="Mechanism"id="Approach1">
<p>To correct the mutation, we are utilizing Prime Editing technologies. Prime Editing is a genome editing technique that allows precise DNA modifications without causing double-strand breaks<SupScrollLinklabel="2"/>. Structurally, the Prime Editing complex consists of a Cas9 endonuclease fused to a reverse transcriptase (RT) and guided by a pegRNA, which directs the complex to the target site in the genome. </p>
<InfoBoxtitle="Prime Editing"id="prime-editing">
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<Collapsibleid="fanzorcas-collapsible"title="Cas vs. Fanzor"> child </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.
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>
<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)<SupScrollLinklabel="6"/>. 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<SupScrollLinklabel="7"/>. Moreover, we use capsaicin in combination with chitosan to improve the uptake of our construct through their mucus-adhesive properties<SupScrollLinklabel="8"/>. </p>
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<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)<SupScrollLinklabel="6"/>. 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<SupScrollLinklabel="7"/>. Moreover, we use capsaicin in combination with chitosan to improve the uptake of our construct through their mucus-adhesive properties<SupScrollLinklabel="8"/>. </p>
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Trocknung <LoremShort/>
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<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<SupScrollLinklabel="9"/>. 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>
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Lagertemperatur der Parts <LoremShort/>
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Trocknung <LoremShort/>
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<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<SupScrollLinklabel="9"/>. 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>
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<Sectiontitle="Our Vision"id="Our Vision">
<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>
