Aug 11, 2026 —
A study published in Molecular Therapy describes a new method that improves adeno-associated virus (AAV) vector production by harnessing the DNA replication machinery of human adenovirus to amplify plasmid DNA inside producer cells.
AAV vectors for gene and cell therapy are typically produced by transfecting large quantities of plasmid DNA into mammalian cells — a step that adds significantly to manufacturing costs and can introduce plasmid-derived contaminants. In the new approach, termed AAVPCR (AAV production with plasmid DNA in cellulo replication), researchers amplified plasmid DNA within HEK293 cells, enabling manufacturing with 10–20-fold less input plasmid while achieving up to 400-fold in-cell amplification to support packaging.
According to the study, the method increased vector yield and full-capsid ratio, reduced plasmid backbone contaminants, and enhanced vector potency up to threefold both in vitro and in vivo. The approach worked across multiple serotypes and transgenes, which the authors suggest could improve the safety, efficacy, and affordability of AAV gene therapies and inform broader gene- and cell-therapy vector manufacturing.
