Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I

摘要: Current strategies for hepatic gene therapy are either quantitatively inefficient or suffer from lack of permanent expression. We have utilized an animal model hereditary tyrosinaemia type I (HT1), a recessive liver disease caused by deficiency fumarylacetoacetate hydrolase (FAH), to determine whether in vivo selection corrected hepatocytes could improve the efficiency transfer. As few as 1,000 transplanted wild-type were able repopulate mutant liver, demonstrating their strong competitive growth advantage. Mutant situ retroviral transfer also positively selected. In animals treated multiple retrovirus injections >90% became FAH positive and function was restored normal. Our results demonstrate that is useful strategy may lead effective treatment human HT1