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用于癌症治疗的RNA干扰

[RNA interference for cancer therapies].

作者信息

Ashihara Eishi

机构信息

Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine and Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.

出版信息

Gan To Kagaku Ryoho. 2010 Nov;37(11):2033-41.

Abstract

RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Selection of appropriate gene targets is an important parameter in the potential success of siRNA cancer therapies. Candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. Importantly, silencing of such genes must not affect the functions of normal cells. Development of suitable drug delivery systems (DDSs) is also an important issue. Numerous methods to transfect siRNAs into cells have been developed, and the use of non-viral DDSs is preferred because it offers greater safety for clinical application than does the use of viral DDSs. In this article, we briefly review the mechanism of RNAi and non-viral DDSs. Next, we discuss some of the most recent findings concerning the administration of siRNAs against polo-like kinase-1 (PLK-1), which regulates the mitotic process in mammalian cells. Finally, several current clinical trials of RNAi therapies against cancers are discussed. Results of current studies and clinical trials demonstrate that manipulation of the RNAi mechanism by use of targeted siRNA offers a novel and attractive therapeutic option against cancer.

摘要

RNA干扰(RNAi)是哺乳动物细胞中一种序列特异性基因沉默现象,其发现使其作为一种强大工具在基因组后研究中得到广泛应用。最近,诱导RNAi的小干扰RNA(siRNA)已被实验性地引入作为一种癌症治疗方法,并有望发展成为一种基于核酸的药物。选择合适的基因靶点是siRNA癌症治疗潜在成功的一个重要参数。候选靶点包括与细胞增殖、转移、血管生成和耐药性相关的基因。重要的是,此类基因的沉默绝不能影响正常细胞的功能。开发合适的药物递送系统(DDS)也是一个重要问题。已经开发出许多将siRNA转染到细胞中的方法,并且非病毒DDS的使用更受青睐,因为与病毒DDS相比,它在临床应用中具有更高的安全性。在本文中,我们简要回顾了RNAi和非病毒DDS的机制。接下来,我们讨论一些关于针对在哺乳动物细胞中调节有丝分裂过程的polo样激酶-1(PLK-1)施用siRNA的最新发现。最后,讨论了当前几项针对癌症的RNAi治疗的临床试验。当前研究和临床试验的结果表明,通过使用靶向siRNA操纵RNAi机制为癌症治疗提供了一种新颖且有吸引力的治疗选择。

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