¹Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, MD, USA

Correspondence: Dr RM Kotin, NHLBI, National Institutes of Health, 10 Center Drive, Building 10, Room 7D18, Bethesda, MD 20817, USA. E-mail: kotinr@nhlbi.nih.gov

Received 24 February 2008; Revised 3 March 2008; Accepted 4 March 2008; Published online 10 April 2008.

Abstract

To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the 'exa-(10¹⁸) scale.' These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome.