Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates

Hum Gene Ther. 2012 Apr;23(4):382-9. doi: 10.1089/hum.2011.200. Epub 2012 Mar 28.


Widespread distribution of gene products at clinically relevant levels throughout the CNS has been challenging. Adeno-associated virus type 9 (AAV9) vector has been reported as a good candidate for intravascular gene delivery, but low levels of preexisting antibody titers against AAV in the blood abrogate cellular transduction within the CNS. In the present study we compared the effectiveness of vascular delivery and cerebrospinal fluid (CSF) delivery of AAV9 in transducing CNS tissue in nonhuman primates. Both delivery routes generated similar distribution patterns, although we observed a more robust level of transduction after CSF delivery. Consistent with previous reports administering AAV9, we found greater astrocytic than neuronal tropism via both routes, although we did find a greater magnitude of CNS transduction after CSF delivery compared with intravascular delivery. Last, we have demonstrated that delivery of AAV9 into the CSF does not shield against AAV antibodies. This has obvious implications when developing and/or implementing any clinical trial studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism*
  • Carotid Arteries
  • Cisterna Magna
  • Dependovirus / genetics*
  • Female
  • Genetic Therapy
  • Genetic Vectors / administration & dosage*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Infusions, Intravenous
  • Macaca fascicularis
  • Macaca mulatta
  • Male
  • Tissue Distribution
  • Transduction, Genetic*


  • Green Fluorescent Proteins