The evolving landscape of recombinant adeno-associated virus (rAAV) manufacturing: Engineering vector plasmids for upstream production.

Engineering vector plasmids and cell lines has significantly enhanced rAAV production, overcoming capacity bottlenecks in the HEK293 system to meet clinical demand.

• Why it matters: Efficient, scalable manufacturing of rAAV vectors is critical for expanding gene therapy applications, but current methods face limitations in yield and scalability that hinder clinical progress.
• What they did: The review explores molecular design improvements in production plasmids, including rep, cap, ITR, and helper genes, along with innovations in plasmid architecture and cell-line engineering, such as inducible and suspension-adapted systems.
• The result: These strategies collectively improve vector productivity, quality, and scalability, paving the way for next-generation, high-yield rAAV manufacturing platforms capable of supporting widespread clinical use.