Adenovirus–mediated in vivo gene transfer and expression in normal rat liver
- 1 August 1992
- journal article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 1 (5), 372-378
- https://doi.org/10.1038/ng0892-372
Abstract
Replication deficient, recombinant adenovirus (Ad) vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in hepatocytes. In vitro, primary cultures of rat hepatocytes infected with a recombinant Ad containing a human alpha 1-antitrypsin cDNA (Ad-alpha 1AT) synthesized and secreted human alpha 1AT for 4 weeks. In rats, in vivo intraportal administration of a recombinant Ad containing the E. coli lacZ gene, was followed by expression of beta-galactosidase in hepatocytes 3 days after infection. Intraportal infusion of Ad-alpha 1AT produced detectable serum levels of human alpha 1AT for 4 weeks. Thus, targeted gene expression has been achieved in the liver, albeit at low levels, suggesting that adenovirus vectors may be a useful means for in vivo gene therapy in liver disorders.Keywords
This publication has 40 references indexed in Scilit:
- Long-Term Improvement of Hypercholesterolemia After Ex Vivo Gene Therapy in LDLR-Deficient RabbitsScience, 1991
- Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC geneFEBS Letters, 1991
- Expression of human α1‐antitrypsin using a recombinant adenovirus vectorFEBS Letters, 1990
- Clinical application of somatic gene therapy in inborn errors of metabolismJournal of Inherited Metabolic Disease, 1990
- Hyperammonemia in Women with a Mutation at the Ornithine Carbamoyltransferase LocusNew England Journal of Medicine, 1990
- INHIBITORS OF THE BIOSYNTHESIS AND PROCESSING OF N-LINKED OLIGOSACCHARIDE CHAINSAnnual Review of Biochemistry, 1987
- Identification of a functional promoter in the long terminal repeat of Rous sarcoma virusCell, 1980
- Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5Journal of General Virology, 1977
- Immunization by selective infection with type 4 adenovirus grown in human diploid tissue cultures. I. Safety and lack of oncogenicity and tests for potency in volunteersJAMA, 1966
- AN ANALYSIS OF MITOSIS IN LIVER RESTORATIONThe Journal of Experimental Medicine, 1937