PMID- 26052519
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150608
LR  - 20201001
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 1
DP  - 2014
TI  - Widespread gene transfer in the central nervous system of cynomolgus macaques 
      following delivery of AAV9 into the cisterna magna.
PG  - 14051
LID - 10.1038/mtm.2014.51 [doi]
AB  - Adeno-associated virus serotype 9 (AAV9) vectors have recently been shown to 
      transduce cells throughout the central nervous system of nonhuman primates when 
      injected into the cerebrospinal fluid (CSF), a finding which could lead to a 
      minimally invasive approach to treat genetic and acquired diseases affecting the 
      entire CNS. We characterized the transduction efficiency of two routes of vector 
      administration into the CSF of cynomolgus macaques-lumbar puncture, which is 
      typically used in clinical practice, and suboccipital puncture, which is more 
      commonly used in veterinary medicine. We found that delivery of vector into the 
      cisterna magna via suboccipital puncture is up to 100-fold more efficient for 
      achieving gene transfer to the brain. In addition, we evaluated the inflammatory 
      response to AAV9-mediated GFP expression in the nonhuman primate CNS. We found 
      that while CSF lymphocyte counts increased following gene transfer, there were no 
      clinical or histological signs of immune toxicity. Together these data indicate 
      that delivery of AAV9 into the cisterna magna is an effective method for 
      achieving gene transfer in the CNS, and suggest that adapting this uncommon 
      injection method for human trials could vastly increase the efficiency of gene 
      delivery.
FAU - Hinderer, Christian
AU  - Hinderer C
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
FAU - Bell, Peter
AU  - Bell P
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
FAU - Vite, Charles H
AU  - Vite CH
AD  - Department of Clinical Studies, School of Veterinary Medicine, University of 
      Pennsylvania , Philadelphia, Pennsylvania, USA.
FAU - Louboutin, Jean-Pierre
AU  - Louboutin JP
AD  - Department of Basic Medical Sciences, Section of Anatomy, University of the West 
      Indies , Kingston, Jamaica.
FAU - Grant, Rebecca
AU  - Grant R
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
FAU - Bote, Erin
AU  - Bote E
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
FAU - Yu, Hongwei
AU  - Yu H
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
FAU - Pukenas, Bryan
AU  - Pukenas B
AD  - Department of Radiology, Hospital of the University of Pennsylvania , 
      Philadelphia, Pennsylvania, USA.
FAU - Hurst, Robert
AU  - Hurst R
AD  - Department of Radiology, Hospital of the University of Pennsylvania , 
      Philadelphia, Pennsylvania, USA.
FAU - Wilson, James M
AU  - Wilson JM
AD  - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University 
      of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA.
LA  - eng
GR  - P40 OD010939/OD/NIH HHS/United States
GR  - P40 RR002512/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20141210
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC4448732
EDAT- 2014/01/01 00:00
MHDA- 2014/01/01 00:01
PMCR- 2014/12/10
CRDT- 2015/06/09 06:00
PHST- 2014/08/22 00:00 [received]
PHST- 2014/09/05 00:00 [accepted]
PHST- 2015/06/09 06:00 [entrez]
PHST- 2014/01/01 00:00 [pubmed]
PHST- 2014/01/01 00:01 [medline]
PHST- 2014/12/10 00:00 [pmc-release]
AID - S2329-0501(16)30120-6 [pii]
AID - 10.1038/mtm.2014.51 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2014 Dec 10;1:14051. doi: 10.1038/mtm.2014.51. 
      eCollection 2014.