Phaneuf D, Hadchouel M, Tanguay R M, Bréchot C, Ferry N
INSERM U370, CHU Necker Enfants Malades, Paris, France.
Biochem Biophys Res Commun. 1995 Mar 28;208(3):957-63. doi: 10.1006/bbrc.1995.1427.
Type I hereditary tyrosinemia results from an inherited deficiency in fumarylacetoacetate hydrolase, the enzyme involved in the last step in tyrosine catabolic pathway. The cloning of the cDNA encoding FAH in human has opened the way to genetic treatment of HT 1. We have constructed recombinant retroviral vectors carrying the cDNA encoding human FAH. In the present report we show that these vectors are able to restore FAH activity stably in primary fibroblasts from HT 1 patients and at high level. The possibility to express FAH stably in deficient patients represents a first step towards future gene therapy for type I hereditary tyrosinemia and may help to decipher the pathogenesis of the disease at the molecular level.
I型遗传性酪氨酸血症是由于遗传性延胡索酰乙酰乙酸水解酶缺乏所致，该酶参与酪氨酸分解代谢途径的最后一步。人类中编码FAH的cDNA的克隆为HT 1的基因治疗开辟了道路。我们构建了携带编码人类FAH的cDNA的重组逆转录病毒载体。在本报告中，我们表明这些载体能够在HT 1患者的原代成纤维细胞中稳定且高水平地恢复FAH活性。在缺陷患者中稳定表达FAH的可能性是I型遗传性酪氨酸血症未来基因治疗的第一步，并且可能有助于在分子水平上解读该疾病的发病机制。
