PMID- 24131981
OWN - NLM
STAT- MEDLINE
DCOM- 20140808
LR  - 20211021
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 21
IP  - 1
DP  - 2014 Jan
TI  - Adeno-associated virus serotypes 9 and rh10 mediate strong neuronal transduction 
      of the dog brain.
PG  - 28-36
LID - 10.1038/gt.2013.54 [doi]
AB  - Canine models have many advantages for evaluating therapy of human central 
      nervous system (CNS) diseases. In contrast to nonhuman primate models, naturally 
      occurring canine CNS diseases are common. In contrast to murine models, the dog's 
      lifespan is long, its brain is large and the diseases affecting it commonly have 
      the same molecular, pathological and clinical phenotype as the human diseases. We 
      compared the ability of four intracerebrally injected adeno-associated virus 
      vector (AAV) serotypes to transduce the dog brain with green fluorescent protein 
      as the first step in using these vectors to evaluate both delivery and efficacy 
      in naturally occurring canine homologs of human diseases. Quantitative measures 
      of transduction, maximum diameter and area, identified both AAV2/9 and AAV2/rh10 
      as significantly more efficient than either AAV2/1 or AAV2/5 at transducing 
      cerebral cortex, caudate nucleus, thalamus and internal capsule. Fluorescence 
      co-labeling with cell-type-specific antibodies demonstrated that AAV2/9 and 
      AAV2/rh10 were capable of primarily transducing neurons, although glial 
      transduction was also identified and found to be more efficient with the AAV2/9 
      vector. These data are a prerequisite to evaluating the efficacy of recombinant 
      AAV vectors carrying disease-modifying transgenes to treat naturally occurring 
      canine models in preclinical studies of human CNS disease therapy.
FAU - Swain, G P
AU  - Swain GP
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Prociuk, M
AU  - Prociuk M
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Bagel, J H
AU  - Bagel JH
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - O'Donnell, P
AU  - O'Donnell P
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Berger, K
AU  - Berger K
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Drobatz, K
AU  - Drobatz K
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Gurda, B L
AU  - Gurda BL
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Haskins, M E
AU  - Haskins ME
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Sands, M S
AU  - Sands MS
AD  - Departments of Internal Medicine and Genetics, Washington University School of 
      Medicine, St Louis, MO, USA.
FAU - Vite, C H
AU  - Vite CH
AD  - Departments of Clinical Studies and Pathobiology, School of Veterinary Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
LA  - eng
GR  - R01 NS084861/NS/NINDS NIH HHS/United States
GR  - P40 RR002512/RR/NCRR NIH HHS/United States
GR  - R01 DK054481/DK/NIDDK NIH HHS/United States
GR  - P40-OD010939/OD/NIH HHS/United States
GR  - R01 HD055461/HD/NICHD NIH HHS/United States
GR  - DK54481/DK/NIDDK NIH HHS/United States
GR  - P40 OD010939/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131017
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/virology
MH  - Caudate Nucleus/metabolism/virology
MH  - Cerebral Cortex/metabolism/virology
MH  - Dependovirus/classification/*genetics/physiology
MH  - Disease Models, Animal
MH  - Dogs
MH  - *Genetic Vectors
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Internal Capsule/metabolism/virology
MH  - Serotyping
MH  - Thalamus/metabolism/virology
MH  - *Transduction, Genetic
MH  - Transgenes
PMC - PMC3881028
EDAT- 2013/10/18 06:00
MHDA- 2014/08/13 06:00
CRDT- 2013/10/18 06:00
PHST- 2013/04/05 00:00 [received]
PHST- 2013/08/23 00:00 [revised]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/10/18 06:00 [entrez]
PHST- 2013/10/18 06:00 [pubmed]
PHST- 2014/08/13 06:00 [medline]
AID - gt201354 [pii]
AID - 10.1038/gt.2013.54 [doi]
PST - ppublish
SO  - Gene Ther. 2014 Jan;21(1):28-36. doi: 10.1038/gt.2013.54. Epub 2013 Oct 17.