HEPATIC GENE-THERAPY - EFFICIENT RETROVIRAL-MEDIATED GENE-TRANSFER INTO RAT HEPATOCYTES IN-VIVO

The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the por tal vein results in 10-15% hepatocyte transduction in vivo. This is 10 times more efficient than in the mouse due partially to the observation that the rat livers have much more synchronous hepatocyte replication after partial hepatectomy. Using a recombinant retroviral vector containing the human alpha(1)-antitrypsin cDNA, persistent expression of the human protein in recipient rat plasma was observed for at least six months and at a level that is 10 times greater than the mouse. Thus, rats can serve as an excellent model for gene therapy of metabolic disorders secondary to hepatic deficiencies.