PMID- 22201473 OWN - NLM STAT- MEDLINE DCOM- 20130624 LR - 20211021 IS - 1557-7422 (Electronic) IS - 1043-0342 (Print) IS - 1043-0342 (Linking) VI - 23 IP - 4 DP - 2012 Apr TI - Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. PG - 382-9 LID - 10.1089/hum.2011.200 [doi] AB - 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. FAU - Samaranch, Lluis AU - Samaranch L AD - Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94103, USA. FAU - Salegio, Ernesto A AU - Salegio EA FAU - San Sebastian, Waldy AU - San Sebastian W FAU - Kells, Adrian P AU - Kells AP FAU - Foust, Kevin D AU - Foust KD FAU - Bringas, John R AU - Bringas JR FAU - Lamarre, Clementine AU - Lamarre C FAU - Forsayeth, John AU - Forsayeth J FAU - Kaspar, Brian K AU - Kaspar BK FAU - Bankiewicz, Krystof S AU - Bankiewicz KS LA - eng GR - 1R01NS073940-01/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120328 PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM CIN - Hum Gene Ther. 2012 Apr;23(4):340-3. PMID: 22490128 MH - Animals MH - Brain/*metabolism MH - Carotid Arteries MH - Cisterna Magna MH - Dependovirus/*genetics MH - Female MH - Genetic Therapy MH - Genetic Vectors/*administration & dosage MH - Green Fluorescent Proteins/genetics/metabolism MH - Infusions, Intravenous MH - Macaca fascicularis MH - Macaca mulatta MH - Male MH - Tissue Distribution MH - *Transduction, Genetic PMC - PMC3327605 EDAT- 2011/12/29 06:00 MHDA- 2013/06/26 06:00 PMCR- 2013/04/01 CRDT- 2011/12/29 06:00 PHST- 2011/12/29 06:00 [entrez] PHST- 2011/12/29 06:00 [pubmed] PHST- 2013/06/26 06:00 [medline] PHST- 2013/04/01 00:00 [pmc-release] AID - 10.1089/hum.2011.200 [pii] AID - 10.1089/hum.2011.200 [doi] PST - ppublish SO - Hum Gene Ther. 2012 Apr;23(4):382-9. doi: 10.1089/hum.2011.200. Epub 2012 Mar 28.