Overturf K, Al-Dhalimy M, Manning K, Ou C N, Finegold M, Grompe M
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Hum Gene Ther. 1998 Feb 10;9(3):295-304. doi: 10.1089/hum.1998.9.3-295.
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.
此前，本实验室已报道利用肝细胞移植和体内基因疗法来纠正遗传性I型酪氨酸血症（HT1）小鼠模型。在此，我们证明了用培养的肝细胞对富马酰乙酰乙酸水解酶（FAH）缺陷型肝脏进行再填充。通过在体外逆转录病毒转导培养的FAH缺陷型肝细胞，然后进行移植和选择性再填充，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已恢复正常。我们的结果表明，使用体外基因操作的肝细胞进行有效的肝脏再填充是可行的。
