Ex vivo hepatic gene therapy of a mouse model of Hereditary Tyrosinemia Type I.
Ex vivo hepatic gene therapy of a mouse model of Hereditary Tyrosinemia Type I.
复制标题
I 型遗传性酪氨酸血症小鼠模型的离体肝基因治疗。
DOI：
10.1089/hum.1998.9.3-295
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发表时间：
1998
影响因子：
4.2
通讯作者：
Grompe,M
中科院分区：
文献类型：
--
作者：
Overturf,K;Al-Dhalimy,M;Manning,K;Ou,CN;Finegold,M;Grompe,M
此前，该实验室已经报道了使用肝细胞移植和活体基因治疗来纠正遗传性酪氨酸血症I型（HT1）小鼠模型。在这里，我们展示了富马酰乙酸水解酶（FAH）缺乏的肝脏与培养的肝细胞的再繁殖。通过在体内逆转录病毒转导培养的FAH¯肝细胞，然后进行移植和选择性再生，实现了疾病表型的纠正。经治疗的小鼠表型正常，血浆氨基酸水平和肝功能测试均得到纠正。我们的研究结果表明，利用体外培养的肝细胞进行肝脏再生是可行的。
Previously, this lab has reported the use of hepatocyte transplantation andin vivogene 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¯ hepatocytesex 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 usingex vivogenetically manipulated hepatocytes is feasible.