In the first project report, the AAVolution team achieved significant advancements in improving AAV vectors for liver gene therapy. As for the approach of gene editing and long-term effects (WP1), we found a promising Cas9 variant to be integrated into AAV vectors, which is effective for gene editing and is currently being tested in living organisms. We also explored ways to make the therapy last longer by investigating units that can autonomously replicate and maintain gene expression.
In addition, regarding the studies on AAV capsids (the carrier of therapeutic genes) (WP2), we created diverse libraries of AAV capsids to find the best ones for effective treatment. We used advanced techniques, including DNA shuffling and rational design, resulting in over 3000 variants. These variants underwent rigorous checks to ensure their quality.
In addressing pre-existing immune response challenges (WP3), we also generated important results. Through innovative approaches, we discovered 48 new Ide molecules, which hold promise in reducing immune responses to the therapy, and developed a machine learning flexible pipeline for designing more Ide. This is crucial for reducing immune responses against AAV therapy.
Overall, the AAVolution team is working to improve liver gene therapy better by using more effective gene-editing tools, exploring ways to make the therapy last longer, and creating diverse libraries of carriers for therapeutic genes. Additionally, the project is also addressing challenges related to the body's immune response to the therapy. These advancements bring hope for more effective and accessible gene therapies in the future.
