Adenovirus-mediated urokinase gene transfer induces liver regeneration and allows for efficient retrovirus transduction of hepatocytes in vivo.
Retrovirus-mediated gene transfer into hepatocytes in vivo results in long-term gene expression. Limitations include the need to remove two-thirds of the liver and the relatively low frequency of gene transfer. To increase gene transfer without surgical hepatectomy, mouse hepatocytes were transduced in vivo with a recombinant adenovirus that transiently expressed urokinase, resulting in high rates of asynchronous liver regeneration. During the regenerative phase, in vivo retroviral-mediated gene transfer in hepatocytes resulted in 5- to 10-fold greater transduction efficiencies than that obtained by conventional partial hepatectomy. In 3-4 weeks, the architecture and microscopic structure of the recipient livers were normal. The two-viral system of achieving permanent transgene expression from hepatocytes in vivo offers an alternative approach to current ex vivo and in vivo gene-transfer models.
Lieber
A
A
Markey Molecular Medicine Center, Department of Medicine, University of Washington, Seattle 98195, USA.
Vrancken Peeters
M J
MJ
Meuse
L
L
Fausto
N
N
Perkins
J
J
Kay
M A
MA
D000256:Adenoviridae; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D000515:alpha 1-Antitrypsin; D001616:beta-Galactosidase; D014568:Urokinase-Type Plasminogen Activator