Scaling-up production of recombinant AAV vectors for clinical applications.

Recombinant adeno-associated virus (AAV)-based vectors capable of expressing therapeutic gene products in vivo have shown significant promise for human gene therapy. A major challenge for these applications is the development of processes to enable production of large quantities of AAV vectors and purification of material that is well characterized and appropriate for parenteral administration. Several cell culture systems have been developed for AAV vector production, and a limited number of these demonstrate the potential to generate AAV vectors at concentrations compatible with cost-effective large-scale production. Vector purification protocols, in particular those based on the use of scalable column chromatography, have concurrently been developed that demonstrate the potential to provide highly purified AAV vector preparations with high yield. These advances support the potential for AAV vectors as therapeutic agents for gene therapy.