Production of AAV Vectors in a Baculovirus Expression System: A Review of Technologies and Approaches

Abstract The adeno-associated vector (AAV) has become a cornerstone in gene therapy, with several approved AAV-based therapeutics successfully used in clinical practice. However, scaling up the production of recombinant AAV (rAAV) remains challenging: the process is still expensive and labor-intensive, which limits the broader availability of gene therapy products. Large-scale rAAV manufacturing can be significantly reduced in cost and simplified by using baculoviruses. Baculovirus expression systems are already employed in the production of at least two approved rAAV-based therapeutics. Baculovirus AAV production platforms continue to improve. Modern systems use a single baculovirus instead of two or three, as well as specialized cell lines. As a result, production efficiency has increased, and the quality of rAAV preparations has improved significantly. This article outlines the history and evolution of various baculovirus systems for rAAV production and describes the most modern and promising platforms for assembling recombinant AAV particles.