Gene transfer to the rhesus monkey brain using SV40-derived vectors is durable and safe

Gene Ther. 2011 Jul;18(7):682-91. doi: 10.1038/gt.2011.13. Epub 2011 Mar 3.


Gene transfer to central nervous system (CNS) has been approached using various vectors. Recombinant SV40-derived vectors (rSV40s) transduce human neurons and microglia effectively in vitro and in rodent brains in vivo, so we tested rSV40s gene transfer to rhesus monkey CNS in vivo, to characterize the distribution, duration and safety of such gene delivery. We used rSV40s carrying HIV-1 RevM10 with a carboxyl-terminal AU1 epitope tag as a marker, and others with the antioxidant enzymes, Cu/Zn superoxide dismutase and glutathione peroxidase. Vectors were injected stereotaxically into the caudate nucleus. Transgene expression was studied at 1 and 6 months by immunostaining serial brain sections. After intraparenchymal administration, numerous transgene-expressing cells were seen, with a longitudinal extent of 20 mm. In neurons and, more rarely, microglial cells, transgene expression remained strong throughout the 6-month study period. Astrocytes and oligodendroglia were not transduced. No evidence of inflammation or tissue damage was observed. SV40-derived vectors may thus be useful for long-term gene expression in the monkey brain and, potentially, in the human brain.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Caudate Nucleus*
  • Gene Transfer Techniques*
  • Genetic Vectors*
  • Glutathione Peroxidase / genetics
  • Macaca mulatta
  • Simian virus 40 / genetics*
  • Simian virus 40 / immunology
  • Superoxide Dismutase / genetics*
  • Transduction, Genetic
  • Transgenes


  • Glutathione Peroxidase
  • Superoxide Dismutase