Mammalian Stable Cell Platforms for Recombinant Adeno-associated Virus (rAAV) Production: Development Strategies and their Impact on Viral Productivity

Abstract

Abstract: Adeno-associated viruses (AAV) are widely used as a recombinant vectors in gene therapy. AAVs are non-pathogenic. They present reduced cytotoxicity and can transduce both dividing and non-dividing cells. The existence of different serotypes provides flexibility for targeting different tissues and organs. Its therapeutic success was already shown by the approval of three products by the European and American regulatory agencies. To satisfy the high dosage, safety, and reproducibility required in each clinical trial, production platforms based on stable mammalian cell lines have been proposed as the best strategy. However, the methodologies employed must be adapted to each cell line, which often results in distinct productivities. In this article, we review the published and commercially available mammalian stable cell lines, discussing the key factors that impact viral production yields, such as integration sites and copy numbers.