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 efficien t method to deliver genes to the rat liver using recombinant retrovira l vectors. A 70% partial hepatectomy followed by retroviral infusion i nto 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 t he observation that the rat livers have much more synchronous hepatocy te replication after partial hepatectomy. Using a recombinant retrovir al vector containing the human alpha(1)-antitrypsin cDNA, persistent e xpression of the human protein in recipient rat plasma was observed fo r 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.