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Journal of Virology, December 1998, p. 10222-10226, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Adeno-Associated Virus as a Vector for Liver-Directed Gene Therapy

Weidong Xiao, Scott C. Berta, Min Min Lu, A. David Moscioni, John Tazelaar, and James M. Wilson*

Institute for Human Gene Therapy and Departments of Molecular and Cellular Engineering and of Medicine, University of Pennsylvania, and the Wistar Institute, Philadelphia, Pennsylvania

Received 10 April 1998/Accepted 2 September 1998

Factors relevant to the successful application of adeno-associated virus (AAV) vectors for liver-directed gene therapy were evaluated. Vectors with different promoters driving expression of human alpha -1-antitrypsin (alpha -1AT) were injected into the portal circulation of immunodeficient mice. alpha -1AT expression was stable but dependent on the promoter. Southern analysis of liver DNA revealed approximately 0.1 to 2.0 provirus copies/diploid genome in presumed head-to-tail concatamers. In situ hybridization and immunohistochemical analysis revealed expression in approximately 5% of hepatocytes clustered in the pericentral region. These results support the use of AAV as a vector for diseases treatable by targeting of hepatocytes.

* Corresponding author. Mailing address: 204 Wistar, 3601 Spruce St., Philadelphia, PA 19104-4268. Phone: (215) 898-3000. Fax: (215) 898-6588. E-mail: wilsonjm{at}mail.med.upenn.edu.

Journal of Virology, December 1998, p. 10222-10226, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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