The baculovirus/insect cell system has proven to be a robust production method for the manufacture of adeno-associated virus (AAV) for gene therapy. It is an attractive method when compared to the triple transfection mammalian process. The baculovirus/insect cell system does not require the production of DNA plasmids, produces a high percentage of full capsids, has similar over all productivities, and is easily scalable. Although the current baculovirus process is adequate for drug manufacturing, it has seen little optimization since it was first introduced to produce recombinant proteins over 20 years ago. Recently there has also been evidence of decreased vector potency some AAV serotypes. Our work has focused on redeveloping the baculovirus/insect cell system to create a highly productive process, producing potent AAV. This has been accomplished by first engineering the baculovirus genome to predictably control AAV viral protein (VP) ratios, resulting in a baculovirus expression system that has the potential to dial-in AAV potency based different protein ratios. We have also focused on increasing overall productivity by addressing bioreactor parameters and media for Sf9 host cell growth, baculovirus infection and AAV production. It is our goal that this work will result in a state-of-the-art process for AAV production on par with current IgG manufacturing in CHO cells.

Achieving a potent AAV using the insect cell/baculovirus system

ACS Fall 2020 Virtual Meeting

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