Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I

Ken Overturf, Muhsen Al-Dhalimy, Ching Nan Ou, Milton Finegold, Robert Tanguay, Andre Lieber, Mark Kay, Markus Grompe

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62 Scopus citations


Mice lacking the enzyme fumarylacetoacetate hydrolase (FAH) have symptoms similar to humans with the disease hereditary tyrosinemia type I (HT1). FAH-deficient mice were injected with a first-generation adenoviral vector expressing the human FAH gene and followed for up to 9 months. Nontreated FAH mutant control mice died within 6 weeks from fulminant liver failure, whereas FAH adenovirus-infected animals survived until sacrifice at 2-9 months. Nine of 13 virus-treated animals developed hepatocellular cancer. Immunohistochemical analysis revealed a mosaic of FAH-deficient and FAH-positive cells in all animals and liver function tests were improved compared to controls. Even mice harvested 9 months after viral infection had > 50% FAH-positive cells. These results demonstrate the strong selective advantage of FAH-expressing cells in an FAH-deficient liver but also illustrate the danger of carcinomas arising from FAH-deficient hepatocytes in HT1.

Original languageEnglish (US)
Pages (from-to)513-521
Number of pages9
JournalHuman Gene Therapy
Issue number5
StatePublished - Mar 20 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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