Insect Cell-Based Recombinant Adeno-Associated Virus Production: Molecular Process Optimization

Abstract

A n increasing number of clinical trials, and the recent approval of the first gene therapy in Europe, alipogene tiparvovec (Glybera®, uniQure), holds promise for recombinant adeno-associated virus (rAAV) to become a mainstay in clinical practice. Since the molecular cloning of AAV in the 1980s, a plethora of production protocols/manufacturing systems for generating rAAV vectors have been developed. uniQure’s manufacturing platform, which has received validation through regulatory approval, is also capable of supporting industrial-scale production based on the baculovirus expression vector system (BEVS) and insect cells. In this paper, we review the molecular process optimization of the various components of uniQure’s rAAV production platform.