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

Gene Ther. 2008 Jun;15(11):823-30. doi: 10.1038/gt.2008.61. Epub 2008 Apr 10.

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-(10(18)) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bioreactors / virology
  • Dependovirus / genetics*
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors / biosynthesis*
  • Genetic Vectors / genetics
  • Humans
  • Industry
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics

Substances

  • Recombinant Proteins