Directed Evolution of AAV Delivery Systems for Clinical Gene Therapy

Learn about the directed evolution approach to engineering adeno-associated virus (AAV) vectors for improved gene therapy applications in this 35-minute webinar presented by Dr. David Schaffer from UC Berkeley. Explore how gene therapy has achieved increasing clinical success with 6 FDA-approved AAV-based products, while understanding the significant barriers that still limit broader therapeutic applications. Discover the challenges facing current AAV vectors, including limited delivery efficiency to target cells, pre-existing antibodies, suboptimal biodistribution, restricted tissue spread, and inability to target specific cell types. Examine why natural viral variants are insufficient for most human diseases and how low efficiencies necessitate high doses that challenge manufacturing processes. Understand the directed evolution methodology that involves iterative genetic diversification of viral genomes and functional selection for desired properties to create highly optimized, next-generation AAV variants. Review successful applications of engineered variants in both animal models and human clinical trials, with specific results and case studies presented. Learn about innovative CRISPR-based genome-wide library screens designed to improve vector yields from manufacturing cell lines. Gain insights from Dr. Schaffer's extensive experience in developing technologies currently used in 9 human clinical trials and his role in founding seven companies, including publicly traded 4D Molecular Therapeutics. Access PACE credits through Labroots registration and completion requirements, with credits available until April 2027.