Finetuning the Vector Factory: Advances in baculovirus-mediated production of gene therapy vectors

Gene therapy offers a promising approach for treating genetic diseases by delivering functional genetic material to target cells, often using viral vectors such as recombinant adeno-associated viruses (rAAVs). Despite their therapeutic potential, large-scale rAAV production remains challenging because the virus is non-autonomous and requires helper-virus functions for replication. The baculovirus expression vector system provides an attractive alternative for production in insect cells, owing to its scalability, compatibility with serum-free suspension culture, and established industrial applications.
This thesis investigates strategies to improve baculovirus-mediated rAAV production, focusing on genetic stability, flexibility of transgene insertion, and interactions between baculovirus and AAV components. Through baculovirus engineering, the studies contribute to more robust and flexible production platforms, including the BAC6Rep system for single-baculovirus-mediated rAAV production. Furthermore, the findings highlight the importance of understanding baculovirus–AAV interactions. These insights support the development of more efficient and reliable rAAV manufacturing processes with improved vector yield, product quality, and consistency.