Advancing AAV production with high-throughput screening and transcriptomics
Christopher A. Reid, Markus Hörer, Mohammad A. Mandegar
Abstract
AAV is a widely used vector for in vivo gene delivery that often requires considerable manufacturing capacity. However, current manufacturing techniques are inefficient, leading to high production costs and product impurities that could limit efficacy and risk patient safety. These factors severely limit the widespread use of AAV-mediated gene therapies for common and rare indications. To develop, manufacture, and commercialize AAV products more efficiently and cost effectively, the manufacturing process needs improvements. Herein, we transcend traditional strategies for developing DoE processes by sharing a new integrated approach that combines high-throughput screening and transcriptomics. This approach can yield proprietary datasets and insight into the mechanisms of AAV production. We also outline how discoveries and innovations in upstream production can be improved to amplify the product yield and quality over the next decade. These efforts will enable the field to fully realize the commercial and therapeutic promise of AAV gene therapies.