Document Detail


Evaluation of adeno-associated viral vectors for liver-directed gene transfer in dogs.
MedLine Citation:
PMID:  21204705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study evaluated six adeno-associated viral (AAV) vectors expressing green fluorescent protein (GFP) from the liver-specific thyroid hormone-binding globulin (TBG) promoter made with novel capsids in canine liver-directed gene transfer. Studies in 1.5-month-old dogs, which were administered vector through a peripheral vein, showed that AAV8 capsid vectors had the most favorable performance profiles. Interestingly, the absolute levels of hepatocyte transduction achieved with AAV8 were lower in dogs compared with what had been achieved in mice and nonhuman primates. Additional studies were performed with AAV8 delivered into the hepatic artery in adult dogs, with higher doses of vector used to assess potential dose-limiting toxicities. These studies showed good transduction on day 7 in one dog that apparently was lost by day 28 in another dog through the generation of GFP-specific T cells. Each adult dog was carefully monitored for any hemodynamic changes associated with vector infusion. Both animals demonstrated mild to moderate hypotension and bradycardia, which appeared to be anesthesia-related, making it difficult to evaluate contributions of the vector.
Authors:
Peter Bell; Guangping Gao; Mark E Haskins; Lili Wang; Meg Sleeper; Huan Wang; Roberto Calcedo; Luk H Vandenberghe; Shu-Jen Chen; Chick Weisse; Elanor Withnall; James M Wilson
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-11
Journal Detail:
Title:  Human gene therapy     Volume:  22     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-23     Completed Date:  2012-03-20     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  985-97     Citation Subset:  IM    
Affiliation:
Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dependovirus / genetics*
Dogs
Gene Transfer Techniques
Genetic Vectors / genetics*
Green Fluorescent Proteins / genetics,  metabolism
Hepatic Artery / metabolism
Liver / blood supply,  metabolism*
T-Lymphocytes, Cytotoxic / metabolism
Grant Support
ID/Acronym/Agency:
DK54481/DK/NIDDK NIH HHS; P30 DK47757/DK/NIDDK NIH HHS; P40 RR02512/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
147336-22-9/Green Fluorescent Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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