Recombinant AAV Production Platforms: Comparative insights for gene therapy manufacturing

Recombinant adeno-associated virus (rAAV) has emerged as a leading platform for gene therapy, leveraging both naturally occurring and engineered capsids to deliver therapeutic transgenes. As clinical and research demand for rAAV has grown, vector quality and manufacturing consistency have become critical considerations. Two production platforms account for the vast majority of clinically relevant rAAV supply: the human embryonic kidney cell line (HEK-293) and the Spodoptera frugiperda (Sf9) insect cell line paired with baculovirus expression vectors. The platforms differ in empty-to-full capsid ratios and process impurities, including encapsidation of host-cell and plasmid DNA. While Sf9 offers advantages in yield, scalability, and manufacturing economics, engineering appropriate capsid protein stoichiometries within the baculovirus system remains a challenge. This review examines these and other key features of each platform as they relate to vector quality and clinical suitability.