Virus-mediated gene transfer to induce therapeutic angiogenesis: Where do we stand?

Virus-mediated gene transfer to induce therapeutic angiogenesis: Where do we stand?
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发表时间:
2007-12
影响因子:
8
通讯作者:
M. Giacca
M. Giacca
中科院分区:
医学2区
文献类型:
--
作者:
M. Giacca

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通过基因转移诱导治疗性血管生成的潜力作为一种可能的组织缺血治疗方法引起了人们的极大兴奋。然而,经过 10 年的临床实验,现在看来,在取得临床成功之前,仍有几个关键问题需要解决。这些包括了解功能性血管是否可能是由于单一血管生成因子的传递而产生的,还是需要更复杂的细胞因子组合,识别治疗基因表达的适当时机,以及最值得注意的是,开发更有效的基因传递工具。基于腺相关病毒(AAV)的病毒载体似乎特别适合满足最后一个要求,因为它们对骨骼肌细胞和心肌细胞表现出特定的趋向性,并无限期地驱动这些细胞中治疗基因的表达。在这篇综述中,我讨论了基因治疗目前在心血管疾病中的应用,特别关注病毒介导的基因转移技术的可能改进。
The potential to induce therapeutic angiogenesis through gene transfer has engendered much excitement as a possible treatment for tissue ischemia. After 10 years of clinical experimentation, however, it now appears clear that several crucial issues are still to be resolved prior to achieving clinical success. These include the understanding of whether functional blood vessels might arise as a result of the delivery of a single angiogenic factor or require more complex cytokine combinations, the identification of the proper timing of therapeutic gene expression and, most notably, the development of more efficacious gene delivery tools. Viral vectors based on the adeno-associated virus (AAV) appear particularly suitable to address the last requirement, since they display a specific tropism for skeletal muscle cells and cardiomyocytes, and drive expression of the therapeutic genes in these cells for indefinite periods of time. In this review, I discuss the current applications of gene therapy for cardiovascular disorders, with particular attention to the possible improvements in the technologies involved in virus-mediated gene transfer.