Adeno-associated virus as a vector for liver-directed gene therapy.
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.
Xiao
W
W
Institute for Human Gene Therapy and Departments of Molecular and Cellular Engineering and of Medicine, University of Pennsylvania, and the Wistar Institute, Philadelphia, Pennsylvania, USA.
Berta
S C
SC
Lu
M M
MM
Moscioni
A D
AD
Tazelaar
J
J
Wilson
J M
JM
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism* / Q000821:virology; D051379:Mice; D014161:Transduction, Genetic; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
D000515:alpha 1-Antitrypsin