A Virus within a Virus – Process Development of an Insect Cell Factory for Gene Therapy

Gene therapy can treat diseases by delivering genetic material into a patient’s cells. Viruses are often used as vehicles for this delivery, but producing enough of these viruses remains challenging and expensive. This PhD research focused on a production method that uses insect cells and baculoviruses, viruses that naturally infect insect cells, to produce recombinant adeno-associated viruses (rAAVs), an important type of gene therapy vector.

The research investigated how baculoviruses infect insect cells and replicate, and how different infection strategies influence the amount and quality of rAAV produced. It also explored a new way to monitor the production process using digital holographic microscopy and machine learning to detect changes in infected insect cells.

The results provide a better understanding of the interactions between insect cells, baculoviruses, and rAAV production. This knowledge can help move the development of these production processes away from mostly trial-and-error optimization towards a more knowledge-based approach.