A largely random AAV integration profile after LPLD gene therapy

Nat Med. 2013 Jul;19(7):889-91. doi: 10.1038/nm.3230. Epub 2013 Jun 16.

Abstract

The clinical application of adeno-associated virus vectors (AAVs) is limited because of concerns about AAV integration-mediated tumorigenicity. We performed integration-site analysis after AAV1-LPL(S447X) intramuscular injection in five lipoprotein lipase-deficient subjects, revealing random nuclear integration and hotspots in mitochondria. We conclude that AAV integration is potentially safe and that vector breakage and integration may occur from each position of the vector genome. Future viral integration-site analyses should include the mitochondrial genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Dependovirus / genetics*
  • Dependovirus / physiology
  • Genetic Therapy* / adverse effects
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Genetic Vectors / physiology
  • Humans
  • Hyperlipoproteinemia Type I / genetics*
  • Injections, Intramuscular
  • Lipoprotein Lipase / administration & dosage
  • Lipoprotein Lipase / deficiency
  • Lipoprotein Lipase / genetics
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Mutagenesis, Insertional / genetics
  • Mutagenesis, Insertional / physiology
  • Transcriptome
  • Virus Integration / genetics
  • Virus Integration / physiology*

Substances

  • Lipoprotein Lipase