Ex vivo hepatic gene therapy of a mouse model of Hereditary Tyrosinemia Type I.

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