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Toward exascale production of recombinant adeno-associated virus for gene transfer applications

Gene Therapy volume 15, pages 823–830 (2008)Cite this article

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.

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Acknowledgements

The Intramural Research Program of the National Heart, Lung, and Blood Institute and NIH supported this work. A Cooperative Research and Development Agreement (CRADA) between Amsterdam Molecular Therapeutics and the NHLBI, the International Collaborative Effort (ICE) for Duchenne Muscular Dystrophy and the Parent Project Muscular Dystrophy (PPMD) provided additional funding.

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

    S Cecchini, A Negrete & R M Kotin

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Correspondence to R M Kotin.

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Cecchini, S., Negrete, A. & Kotin, R. Toward exascale production of recombinant adeno-associated virus for gene transfer applications. Gene Ther 15, 823–830 (2008). https://doi.org/10.1038/gt.2008.61

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