AAV Capsid Generation Platform for Enhanced Delivery and Specificity
Enthusiasm for gene therapies to treat chronic, life-threatening and debilitating diseases is surging. However, a major obstacle for successful gene-therapy treatment remains: achieving efficient delivery of therapeutic DNA in vivo. The adeno-associated virus (AAV) capsid is now the predominant method for in vivo delivery, but its efficiency is limited by the tendency of natural virus capsids to reach off-target tissues, as well as the effects of neutralizing antibodies against the therapy. George Church's lab has engineered the next generation of AAV capsids to enhance delivery, tissue specificity, and immune evasion for improved clinical efficacy. The technology has dramatically accelerated the directed evolution of AAV capsids in animal models using a combination of DNA synthesis, next-generation DNA sequencing, and machine learning. This platform enables the testing of hundreds of thousands of different capsids across multiple tissues and assays in parallel to optimize capsids for clinical delivery. Dyno Therapeutics, a startup emerging from the Church Lab based on this foundational technology, aims to commercialize this AAV capsid-generation platform, identifying biopharma partners in order to access diverse therapeutic opportunities.