In vivo retroviral-mediated transfer of a marker-gene in ornithine transcarbamylase-deficient Spf(ash) mice.

Gene therapy is a new therapeutic approach for inherited metabolic hepatopathies. The authors studied the potential application of such a strategy to the correction of ornithine transcarbamylase (OTC) deficiency by in vivo protocol of retroviral-mediated gene transfer to the liver. A partial hepatectomy was followed (24 to 48 hours later) by asanguinous perfusion of the regenerating liver with beta-galactosidase (beta-gal) recombinant retrovirus. This protocol allowed beta-gal gene transfer in normal C57B6 mice liver with 60 +/- 52 positive cells per square centimeter. This proportion never exceeded 20 cells per square centimeter in OTC-deficient spf(ash) mice. The high mortality rate for spf(ash) mice was explained by an important sensitivity of those mice to the protein catabolism rather than by technical difficulties during intraportal perfusion. This first in vivo retroviral-mediated gene transfer study in animals with a life-threatening metabolic inherited hepatopathy showed that, despite efficiency of gene therapy in normal animal models, several experimental difficulties should be overcome before human application of this protocol is considered