Document Type

Journal Article

Date of this Version

8-22-2011

Publication Source

Human Gene Therapy

Volume

22

Issue

8

Start Page

985

Last Page

997

DOI

10.1089/hum.2010.194

Abstract

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.

Copyright/Permission Statement

This is a copy of an article published in Human Gene Therapy © 2011 [copyright Mary Ann Liebert, Inc.]; Human Gene Therapy is available online at: http://www.liebertonline.com.

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Date Posted: 24 July 2013

This document has been peer reviewed.