Hepatic Gene Therapy: Persistent Expression of Human α1-Antitrypsin in Mice after Direct Gene Delivery In Vivo
Hepatic Gene Therapy: Persistent Expression of Human α1-Antitrypsin in Mice after Direct Gene Delivery In Vivo
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肝脏基因治疗：体内直接基因递送后人α1-抗胰蛋白酶在小鼠体内持续表达
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
S. Woo
中科院分区：
文献类型：
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作者：
M. Kay;Qiutang Li;T. Liu;F. Leland;C. Toman;M. Finegold;S. Woo
摘要肝脏是基因治疗的理想靶器官。目前肝基因治疗的策略包括从切除的肝叶中分离原代肝细胞，体外转导治疗基因，然后自体肝细胞移植。这种离体方法在整体上是一个相当复杂的过程;因此，已经开发了一种用于将基因直接递送到体内肝细胞中的简单方法。该手术包括部分肝切除术，然后通过门静脉输注重组逆转录病毒载体。在体内递送携带E.大肠杆菌（β-半乳糖苷酶基因）的转染结果显示，有1-2%的实质细胞被转导。在白蛋白启动子-增强子的转录指导下，人α1-抗胰蛋白酶cDNA的直接肝转移导致人蛋白在受体血清中以30- 1，400 ng/ml的浓度组成型表达至少6个月。那个...
ABSTRACT The liver represents an excellent target organ for gene therapy. The current strategy for hepatic gene therapy involves the isolation of primary hepatocytes from a resected liver lobe, transduction of therapeutic genes in vitro followed by autologous hepatocellular transplantation. This ex vivo approach is a rather complex procedure in its entirety; thus, a simple method for direct gene delivery into hepatocytes in vivo has been developed. The procedure involves partial hepatectomy followed by the portal vein infusion of recombinant retroviral vectors. Histological analysis of hepatocytes after in vivo delivery of a recombinant retrovirus bearing the E. coli (β-galactosidase gene showed that 1–2% of the parenchymal cells were transduced. Direct hepatic transfer of human α1-antitrypsin cDNA under the transcriptional direction of the albumin promoter–enhancer led to constitutive expression of the human protein in the sera of recipients at concentrations of 30–1,400 ng/ml for at least 6 months. The ...