EX-VIVO HEPATIC GENE-THERAPY OF A MOUSE MODEL OF HEREDITARY TYROSINEMIA TYPE-I

Previously, this lab has reported the use of hepatocyte transplantatio n and in vivo gene therapy for the correction of a mouse model of Here ditary Tyrosinemia Type I (HT1), Here, we demonstrate repopulation of fumarylacetoacetate hydrolase (FAH)-deficient livers with cultured hep atocytes. Correction of the disease phenotype was achieved by retrovir ally transducing cultured FAH-hepatocytes ex vivo, followed by transpl antation and selective repopulation, Treated mice were phenotypically normal and had corrected plasma amino acid levels and liver function t ests, Our results demonstrate that efficient hepatic repopulation usin g ex vivo genetically manipulated hepatocytes is feasible.