Plasmid Engineering To Improve AAV Productivity And Packaging Efficiency

The packaging efficiency (full to total capsid ratio, or F/T ratio) for Adeno-Associated Virus (AAV) is a critical quality attribute for the manufacturing and commercialization of AAV-based gene therapies. A higher F/T ratio has the potential for reducing dosage and eventually the cost of goods (COGs). In this study, we present design improvements in pHelper and pRepCap plasmids that an support increased AAV titers, whilst improving F/T ratio in upstream crude harvest using a triple plasmid transfection process. The data presented shows significant performance improvement. This study demonstrates that we can significantly increase the AAV productivity and packaging efficiency for various AAV serotypes and client-specific Genes of Interest (GOIs) at the upstream production stage through plasmid engineering approaches.