<p>In conclusion, the entrepreneurial journey of developing RNA-based gene therapy for Cystic Fibrosis, as outlined in our experiences and interviews with industry founders, demonstrates that entrepreneurship is not only an interesting possibility but a necessary avenue to transform scientific innovation into real-world solutions. Our approach has been shaped by the challenges and opportunities in the biotech field, from understanding regulatory frameworks like GxP to navigating complex market dynamics and funding challenges. </p>
<p>Through key interviews, such as the one with Nicole Friedlein, we have gained insights into the pivotal role of regulatory standards in scaling our project. The completion of GxP training by one team member reflects our commitment to ensuring compliance with Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP), both of which are essential for advancing from proof-of-concept to clinical trials. This foundation is crucial for building investor confidence and meeting regulatory requirements.</p>
<p>Additionally, market evaluations reveal a significant opportunity for our therapy, particularly targeting the unmet needs of Cystic Fibrosis patients who do not respond to current treatments like CFTR modulators. The growing gene therapy market presents a strong case for our innovation, although we are aware of the competitive landscape dominated by companies like Vertex Pharmaceuticals. Our unique value lies in providing a more permanent solution for patients not served by existing treatments. </p>
<p>Interviews with founders from companies such as PlasmidFactory and RNhale have provided valuable lessons on transitioning from research to commercialization. The importance of building networks, securing diverse funding sources, and maintaining flexibility to adapt to market feedback are key takeaways that will guide our next steps. Establishing strategic partnerships and seeking early engagement with regulatory bodies will be essential as we prepare for clinical trials and eventual market entry.</p>
<p>To align our long-term vision of revolutionizing Cystic Fibrosis treatment with immediate milestones, we will continue optimizing our lipid nanoparticle delivery system, pursuing regulatory compliance, and engaging with the Cystic Fibrosis community to refine our product. Our focus on both the scientific and business aspects ensures that we are building a strong foundation for success in bringing this innovative therapy to market, improving the lives of patients with Cystic Fibrosis. </p>
<p>“The product composition will depend on the enzyme missing or malfunctioning in each of the disease types. We’re going to target autosomal recessive congenital ichthyosis, as this is the one our friend is struggling with. We will focus on the consequences of mutations in three different genes (TGM1, ALOXE3, ALOX12B) that can underlie this condition [5]. However, if our approach turns out to be successful, after some adjustments, the protocol could be applied for the remaining types of the disease as well. First of all, we’ll engineer E. coli to produce the chosen enzymes encoded by the corresponding genes we chose: transglutaminase 1, Epidermis-type lipoxygenase 3, Arachidonate 12-lipoxygenase and then we will purify them from the bacteria. Once this system is established and optimized, we’ll proceed to design a functioning delivery system that we will encapsulate the enzymes in. We have decided to produce modulated liposomes that will be able to keep the enzymes active while transporting them. Once the target skin layer is reached, the liposomes will fuse with the membranes of the cells of interest, delivering the product to its final destination. Functioning liposomes packed with the produced enzymes will then be incorporated into a suitable medium to facilitate the topical application for the patients”. </p>
<H4text="iGEM team Liu project our idea"/>
<p>We first made contact with the team of LIU via email, due to both our teams’ interest in working with LNP based delivery systems. It rapidly became apparent that our two teams could benefit from a corporation especially since the team of LiU was working on an LNP handbook at the time.</p>
<p>Early in our project, we faced challenges working with human biomaterials, particularly cultivating primary human nasal epithelial cells from both CF patients and controls. To address these, we made three key contributions:</p>
<ol>
<li>A guideline for handling biomaterials in compliance with BSL2 standards.{/* [Link guideline] */}</li>
...
...
@@ -63,16 +50,23 @@ export function HPCollabs(){
These frameworks ensure that future iGEM teams can overcome similar challenges, ensuring safety and regulatory compliance while streamlining their workflow.
We contributed an extensive collection of optimized protocols for future iGEM teams, integrating our experiences to make synthetic biology more accessible. By embedding safety standards, we enable teams to confidently work with human biomaterials, ensuring regulatory compliance and efficient progress.
</p>
<H5text="PreCL Reporter System "/>
<p>To test Prime Editing systems targeting the CF-specific delF508 mutation, we developed the PreCL reporter system [Link engineering of PreCL], which offers high sensitivity, minimal noise, and precise fluorescence detection. This versatile tool, adaptable for CRISPR and base editing, enhances the precision of genetic research, particularly in CF studies.
We optimized pegRNA design{/* [linkpegrna] */} by incorporating the TevoPreQ1 RNA motif, improving stability and Prime Editing efficiency. Our innovations, including silent edits and fine-tuned sequences, boost editing accuracy, providing a robust tool for genetic research. </p>
<H5text="Prime Editing Technology PrimeGuide & Lipid Nanoparticle System AirBuddy "/>
<p>Our PrimeGuide{/* [link] */}system introduces a novel eukaryotic RNA-binding DNA-nickase, a smaller alternative to Cas9. Enhanced with a more efficient Reverse Transcriptase and optimized RNA-binding proteins, this advancement improves Prime Editing accuracy and safety for genetic mutation correction.
We developed AirBuddy{/* [link] */}, a lung-specific RNA/DNA delivery system optimized for gene therapies targeting lung diseases. With low cytotoxicity, efficient cellular uptake, and cost-effective storage, AirBuddy revolutionizes lung disease treatments by providing a safer and more effective delivery method. </p>
<H5text="Wiki Development"/>
<p>To support future iGEM teams, we developed troubleshooting guides for HTML and CSS{/* [link] */}, making wiki development more accessible and easier to manage.
Through these contributions, we provide valuable tools and frameworks to advance synthetic biology, ensuring safer, more efficient research and therapeutic development for the iGEM community. </p>
<H5text="PreCL Reporter System "/>
<p>To test Prime Editing systems targeting the CF-specific delF508 mutation, we developed the PreCL reporter system [Link engineering of PreCL], which offers high sensitivity, minimal noise, and precise fluorescence detection. This versatile tool, adaptable for CRISPR and base editing, enhances the precision of genetic research, particularly in CF studies.
We optimized pegRNA design{/* [linkpegrna] */} by incorporating the TevoPreQ1 RNA motif, improving stability and Prime Editing efficiency. Our innovations, including silent edits and fine-tuned sequences, boost editing accuracy, providing a robust tool for genetic research. </p>
<H5text="Prime Editing Technology PrimeGuide & Lipid Nanoparticle System AirBuddy "/>
<p>Our PrimeGuide{/* [link] */}system introduces a novel eukaryotic RNA-binding DNA-nickase, a smaller alternative to Cas9. Enhanced with a more efficient Reverse Transcriptase and optimized RNA-binding proteins, this advancement improves Prime Editing accuracy and safety for genetic mutation correction.
We developed AirBuddy{/* [link] */}, a lung-specific RNA/DNA delivery system optimized for gene therapies targeting lung diseases. With low cytotoxicity, efficient cellular uptake, and cost-effective storage, AirBuddy revolutionizes lung disease treatments by providing a safer and more effective delivery method. </p>
<H5text="Wiki Development"/>
<p>To support future iGEM teams, we developed troubleshooting guides for HTML and CSS{/* [link] */}, making wiki development more accessible and easier to manage.
Through these contributions, we provide valuable tools and frameworks to advance synthetic biology, ensuring safer, more efficient research and therapeutic development for the iGEM community. </p>
