Retroviral vector-mediated gene transfer into endothelial cells.

Molecular biology & medicine Pub Date : 1991-04-01
D A Dichek
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Abstract

Over the last few years several groups have used retroviral vectors to achieve stable gene transfer into endothelial cells. In vitro experiments include transduction of cultured cells with genes of potential therapeutic interest, such as growth hormone and tissue plasminogen activator (t-PA). Animal studies have demonstrated the feasibility of in vivo recombinant gene expression from transduced endothelial cells, but have thus far been accomplished only with the lacZ marker gene. All studies to date have been oriented primarily toward the use of transduced endothelial cells to provide gene therapy. Numerous issues remain to be addressed with experimental data prior to the initiation of a clinical protocol using transduced endothelial cells. These issues include the introduction of larger numbers of transduced cells into the vasculature and the achievement of appropriate regulation of transgene expression. The use of retroviral vectors to study basic endothelial cell biology has been relatively ignored. The tool of retroviral vector-mediated gene transfer is available for use in answering both therapeutic and pathophysiological questions in endothelial cell biology.

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逆转录病毒载体介导的内皮细胞基因转移。
在过去的几年中,一些研究小组利用逆转录病毒载体将基因稳定地转移到内皮细胞中。体外实验包括培养细胞与潜在的治疗兴趣基因的转导,如生长激素和组织纤溶酶原激活剂(t-PA)。动物研究已经证明了从转导的内皮细胞中表达体内重组基因的可行性,但迄今为止只完成了lacZ标记基因的表达。迄今为止,所有的研究都主要是针对使用转导内皮细胞来提供基因治疗。在使用转导内皮细胞的临床方案开始之前,仍有许多问题需要用实验数据来解决。这些问题包括引入大量的转导细胞进入脉管系统和实现转基因表达的适当调节。利用逆转录病毒载体研究基本内皮细胞生物学一直相对被忽视。逆转录病毒载体介导的基因转移工具可用于回答内皮细胞生物学中的治疗和病理生理问题。
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