Adenovirus-mediated urokinase gene transfer induces liver regeneration and allows for efficient retrovirus transduction of hepatocytes in vivo.

Adenovirus-mediated urokinase gene transfer induces liver regeneration and allows for efficient retrovirus transduction of hepatocytes in vivo.
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腺病毒介导的尿激酶基因转移诱导肝再生,并允许体内肝细胞有效的逆转录病毒转导。

DOI:
10.1073/pnas.92.13.6210
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发表时间:
1995
影响因子:
11.1
通讯作者:
Kay,MA
Kay,MA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lieber,A;VranckenPeeters,MJ;Meuse,L;Fausto,N;Perkins,J;Kay,MA

文献摘要

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逆转录病毒介导的基因转移到体内肝细胞中导致长期基因表达。其局限性包括需要切除三分之二的肝脏以及基因转移的频率相对较低。为了增加基因转移而无需手术肝切除术,小鼠肝细胞在体内转导的重组腺病毒,瞬时表达尿激酶,导致高速率的异步肝再生。在再生阶段,在体内逆转录病毒介导的基因转移在肝细胞中导致5- 10倍以上的转导效率比传统的部分肝切除术。3-4周时,受体肝脏的结构和显微结构基本正常。在体内实现从肝细胞永久转基因表达的双病毒系统为当前离体和体内基因转移模型提供了替代方法。
Retrovirus-mediated gene transfer into hepatocytes in vivo results in long-term gene expression. Limitations include the need to remove two-thirds of the liver and the relatively low frequency of gene transfer. To increase gene transfer without surgical hepatectomy, mouse hepatocytes were transduced in vivo with a recombinant adenovirus that transiently expressed urokinase, resulting in high rates of asynchronous liver regeneration. During the regenerative phase, in vivo retroviral-mediated gene transfer in hepatocytes resulted in 5- to 10-fold greater transduction efficiencies than that obtained by conventional partial hepatectomy. In 3-4 weeks, the architecture and microscopic structure of the recipient livers were normal. The two-viral system of achieving permanent transgene expression from hepatocytes in vivo offers an alternative approach to current ex vivo and in vivo gene-transfer models.