PMID- 26824881
OWN - NLM
STAT- MEDLINE
DCOM- 20170206
LR  - 20181113
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 23
IP  - 5
DP  - 2016 May
TI  - Intracerebroventricular delivery of self-complementary adeno-associated virus 
      serotype 9 to the adult rat brain.
PG  - 401-7
LID - 10.1038/gt.2016.6 [doi]
AB  - Gene therapy for the central nervous system is poised to become a powerful 
      treatment for numerous neurological disorders. Adeno-associated viral vectors 
      based on serotype 9 (AAV9) have proven themselves to be strong candidates for 
      delivering gene-based therapies throughout the brain and spinal cord when 
      administered intravenously, intrathecally, intracisternally, and 
      intracerebroventricularly (i.c.v.). Previous studies of i.c.v.-delivered 
      self-complimentary AAV9 have been performed in neonatal mice with delivery of a 
      single dose. However, before clinical trials can be considered, more information 
      is required about the dose-response relationship for transduction efficiency in 
      adult animals. In the current study, three doses of self-complementary AAV9 were 
      administered to adult rats. High levels of transduction were observed in the 
      hippocampus, cerebellum and cerebral cortex, and transduction increased with 
      increasing dosage. Both neurons and astrocytes were transduced. There was no 
      evidence of astrocytosis at the doses tested. Preliminary results from pigs 
      receiving i.c.v. self-complementary AAV9 are also presented. The results of this 
      study will serve to inform dosing studies in large animal models before clinical 
      testing.
FAU - Donsante, A
AU  - Donsante A
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - McEachin, Z
AU  - McEachin Z
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - Riley, J
AU  - Riley J
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - Leung, C H
AU  - Leung CH
AD  - Department of Biology, Widener University, Chester, PA, USA.
FAU - Kanz, L
AU  - Kanz L
AD  - Department of Biology, Widener University, Chester, PA, USA.
FAU - O'Connor, D M
AU  - O'Connor DM
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 
      USA.
FAU - Boulis, N M
AU  - Boulis NM
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20160129
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Cerebellum/metabolism
MH  - Cerebral Cortex/metabolism
MH  - Dependovirus/*genetics
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Gliosis/genetics
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Infusions, Intraventricular
MH  - Mice
MH  - Neurons/metabolism
MH  - Rats
MH  - Serogroup
MH  - Swine
MH  - *Transduction, Genetic
EDAT- 2016/01/30 06:00
MHDA- 2017/02/07 06:00
CRDT- 2016/01/30 06:00
PHST- 2015/05/07 00:00 [received]
PHST- 2015/12/08 00:00 [revised]
PHST- 2016/01/13 00:00 [accepted]
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2017/02/07 06:00 [medline]
AID - gt20166 [pii]
AID - 10.1038/gt.2016.6 [doi]
PST - ppublish
SO  - Gene Ther. 2016 May;23(5):401-7. doi: 10.1038/gt.2016.6. Epub 2016 Jan 29.