HBV-derived promoters direct liver-specific expression of an adenovirally transduced LDL receptor gene

Item Type:	Article
Title:	HBV-derived promoters direct liver-specific expression of an adenovirally transduced LDL receptor gene
Creators Name:	Sandig, V. and Loeser, P. and Lieber, A. and Kay, M.A. and Strauss, M.
Abstract:	In vivo approaches to liver gene therapy will require restriction of transgene expression to hepatocytes. Since targeting of viral vectors exclusively to the liver is not easy to achieve, use of liver-specific promoters for driving expression of therapeutic genes is an interesting alternative. We have shown previously that regulatory elements of the hepatotrophic hepatitis B virus (HBV) are strong and liver-specific in vitro and therefore might be useful in hepatic gene therapy. Here we describe recombinant adenoviruses in which the human LDL receptor gene is under the transcriptional control of the HBV core promoter, the core promoter linked directly to HBV enhancer I, or a HBV-CMV hybrid promoter, respectively. These viruses allowed for a moderate to strong expression of the LDL receptor gene in vitro in a hepatocyte-specific manner when compared with the CMV immediate-early promoter. In vivo experiments demonstrated that the promoter gave rise to an expression level comparable to that from the CMV promoter in mouse liver, but was very weak in lung and skeletal muscle. Thus, the HBV-CMV hybrid promoter is strong and hepatocyte specific both in vitro and in vivo even in the adenoviral context and would be a good choice for driving a therapeutic gene in liver gene therapy.
Keywords:	Adenovirus, Liver, HBV Promoters, Liver-Specific Gene Expression, LDL Receptor, Animals, Mice
Source:	Gene Therapy
ISSN:	0969-7128
Publisher:	Nature Publishing Group
Volume:	3
Number:	11
Page Range:	1002-1009
Date:	October 1996
PubMed:	View item in PubMed

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