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 hep atopathies. The authors studied the potential application of such a st rategy to the correction of ornithine transcarbamylase (OTC) deficienc y by in vivo protocol of retroviral-mediated gene transfer to the live r. A partial hepatectomy was followed (24 to 48 hours later) by asangu inous perfusion of the regenerating liver with beta-galactosidase (bet a-gal) recombinant retrovirus. This protocol allowed beta-gal gene tra nsfer in normal C57B6 mice liver with 60 +/- 52 positive cells per squ are centimeter. This proportion never exceeded 20 cells per square cen timeter in OTC-deficient spf(ash) mice. The high mortality rate for sp f(ash) mice was explained by an important sensitivity of those mice to the protein catabolism rather than by technical difficulties during i ntraportal perfusion. This first in vivo retroviral-mediated gene tran sfer study in animals with a life-threatening metabolic inherited hepa topathy showed that, despite efficiency of gene therapy in normal anim al models, several experimental difficulties should be overcome before human application of this protocol is considered. Copyright (C) 1996 by W.B. Saunders Company.