Optimization of recombinant adeno-associated virus production using an herpes simplex virus amplicon system

J Virol Methods. 2001 Aug;96(2):97-105. doi: 10.1016/s0166-0934(01)00298-1.

Abstract

A major limitation of adeno-associated virus (AAV) based vectors for clinical applications to date is the production of high-titer recombinant AAV vector stocks. Despite recent improvements, the amount of recombinant adeno-associated virus vectors (rAAV) particles produced per cell continues to be significantly lower than that of wild-type AAV. In this study, an HSV-based system for rAAV production was used to examine the influence of different parameters including transfection conditions (vector-to-packaging plasmid ratio, amount of total transfected DNA, cell confluency) and multiplicity of infection of herpes helper virus on the resulting titre of rAAV stocks. For herpes helper virus, time-course experiments were carried out to analyse the effect on rAAV yields up to 72 h postinfection and to determine the ideal harvesting time. Taken together, the optimized production scheme consistently yields more than 3x10(3) transducing units per producer cell.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA, Viral
  • Dependovirus / genetics*
  • Dependovirus / physiology*
  • Genetic Therapy / methods
  • Genetic Vectors*
  • HeLa Cells
  • Helper Viruses / genetics*
  • Helper Viruses / physiology
  • Humans
  • Plasmids / genetics
  • Recombination, Genetic / genetics
  • Simplexvirus / genetics*
  • Simplexvirus / pathogenicity
  • Simplexvirus / physiology
  • Transduction, Genetic
  • Transfection
  • Virus Cultivation
  • Virus Replication

Substances

  • DNA, Viral