Molecular Therapy: Methods & Clinical Development (Jan 2014)

Aurintricarboxylic acid increases yield of HSV-1 vectors

  • Peter Pechan,
  • Jeffery Ardinger,
  • Jyothi Ketavarapu,
  • Hillard Rubin,
  • Samuel C Wadsworth,
  • Abraham Scaria

DOI
https://doi.org/10.1038/mtm.2013.6
Journal volume & issue
Vol. 1, no. C

Abstract

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Production of large quantities of viral vectors is crucial for the success of gene therapy in the clinic. There is a need for higher titers of herpes simplex virus-1 (HSV-1) vectors both for therapeutic use as well as in the manufacturing of clinical grade adeno-associated virus (AAV) vectors. HSV-1 yield increased when primary human fibroblasts were treated with anti-inflammatory drugs like dexamethasone or valproic acid. In our search for compounds that would increase HSV-1 yield, we investigated another anti-inflammatory compound, aurintricarboxylic acid (ATA). Although ATA has been previously shown to have antiviral effects, we find that low (micromolar) concentrations of ATA increased HSV-1 vector production yields. Our results showing the use of ATA to increase HSV-1 titers have important implications for the production of certain HSV-1 vectors as well as recombinant AAV vectors.