Advancements in Insect-Cell Baculovirus Expression Vector Platform for
Production of Recombinant Adeno-Associated Virus-Based Gene Delivery
Vectors
Abstract
Despite rapid progress in the field, scalable high-yield production of
AAV is still one of the critical bottlenecks the manufacturing sector is
facing. The insect cell-baculovirus expression vector system (IC-BEVS)
has emerged as a mainstream platform for a scalable production of
recombinant proteins with clinically approved products for human use. In
this review, we provide a detailed overview on advancements in IC-BEVS
for rAAV production. Since the first report of baculovirus induced
production of rAAV in insect cells in 2002, this platform has undergone
significant evolutions. The original three baculovirus system was
improved to enhance expression stability and further streamlined to
reduce the number of baculoviruses to two and eventually one. The one
baculovirus system consisting of an inducible packaging insect cell line
was further improved to enhance the AAV vector quality and potency. In
parallel, implementation of advanced manufacturing approaches and
control of critical processing parameters have demonstrated promising
results with process validation in large scale bioreactor runs.
Moreover, optimization of molecular design of vectors to enable higher
cell-specific yield of functional AAV particles in combination with
bioprocess intensification strategies may further contribute to
addressing current and future manufacturing challenges.