Streamline AAV-Based Gene Therapies With High-Performing Off-The-Shelf Plasmids

By George Buchman and Bhargavi Kondragunta, Catalent

Plasmids, which encode the genetic components necessary for viral replication, packaging, and gene expression, are essential starting materials in viral vector production. In adeno-associated virus (AAV) manufacturing, triple transfection typically uses three plasmids—Rep/Cap, pHelper, and the gene of interest (GOI)—to produce vectors for delivering therapeutic genes. The quality and optimization of these plasmids strongly influence yield, efficiency, and product consistency. To meet growing demand for AAV-based therapies, the industry increasingly relies on standardized, well-characterized off-the-shelf (OTS) plasmids paired with platform manufacturing processes. These approaches simplify supply chains, reduce development timelines, and enable reproducibility, while supporting regulatory compliance.

Well-controlled, scalable processes ensure consistent performance across batches and can be adapted for both common and novel viral vector serotypes. Characterization tools, such as next-generation sequencing and orthogonal validation methods, help confirm sequence stability and product integrity. Similar principles apply to other viral vector modalities, such as lentiviral vectors, where safety and scalability are equally critical. By integrating high-quality plasmids with proven process controls, developers can more efficiently transition from preclinical research to commercial production. This model supports rapid, reliable manufacturing of viral vectors, advancing gene therapy development and enabling timely delivery of innovative treatments to patients.