RNA interference technologies and therapeutics: from basic research to products.
RNA interference technologies and therapeutics: from basic research to products.
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DOI：
10.2165/11318190-000000000-00000
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Jiménez A
中科院分区：
文献类型：
--
作者：
López-Fraga M;Martínez T;Jiménez A
RNA 干扰 (RNAi) 是一种自然细胞过程，通过降解特定信使 RNA 或阻断翻译，在翻译阶段通过高度精确的序列定向基因沉默机制来调节基因表达。近年来，RNAi 在治疗应用中的应用获得了相当大的发展势头。有人认为，大多数已确定的新的疾病相关靶标不能用传统方法“药物化”。然而，任何致病基因和任何细胞类型或组织都可能成为 RNAi 的目标。本综述重点关注 RNAi 机制的当前知识以及与其在治疗环境中的潜在用途相关的安全问题。在临床环境中应用基于 RNAi 的产品时，需要考虑的一些最重要的方面与通过仔细设计核酸序列和引入化学修饰来实现高功效和增强稳定性有关，但最重要的是，与开发改进的病毒和非病毒递送系统有关。这些新的递送系统允许这些产品以高度特异性的方式并在施用尽可能低的剂量后到达所需的靶细胞、组织或器官。目前正在研究各种应用途径和目标位置，以便开发针对不同目标和病理的有效递送系统，包括感染性病理、遗传病理和与内源性 microRNA 失调相关的疾病。与任何新技术一样，在临床干预的道路上出现了一些挑战和需要考虑的重要方面，例如。临床前毒理学研究、监管问题和知识产权保护的正确设计。回顾了与在临床环境中使用基于 RNAi 的产品相关的主要优势，以及使用这些化合物的最新临床和临床前研究。
RNA interference (RNAi) is a natural cellular process that regulates gene expression by a highly precise mechanism of sequence-directed gene silencing at the stage of translation by degrading specific messenger RNAs or blocking translation. In recent years, the use of RNAi for therapeutic applications has gained considerable momentum. It has been suggested that most of the novel disease-associated targets that have been identified are not ‘druggable’ with conventional approaches. However, any disease-causing gene and any cell type or tissue can potentially be targeted with RNAi. This review focuses on the current knowledge of RNAi mechanisms and the safety issues associated with its potential use in a therapeutic setting. Some of the most important aspects to consider when working towards the application of RNAi-based products in a clinical setting have been related to achieving high efficacies and enhanced stability profiles through a careful design of the nucleic acid sequence and the introduction of chemical modifications, but most of all, to developing improved delivery systems, both viral and non-viral. These new delivery systems allow for these products to reach the desired target cells, tissues or organs in a highly specific manner and after administration of the lowest possible doses. Various routes of application and target locations are currently being addressed in order to develop effective delivery systems for different targets and pathologies, including infectious pathologies, genetic pathologies and diseases associated with dysregulation of endogenous microRNAs. As with any new technology, several challenges and important aspects to be considered have risen on the road to clinical intervention, e.g. correct design of preclinical toxicology studies, regulatory concerns, and intellectual property protection. The main advantages related to the use of RNAi-based products in a clinical setting, and the latest clinical and preclinical studies using these compounds, are reviewed.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
DOI：
10.1016/s0006-291x(02)02013-2
发表时间：
2002-08-30
影响因子：
3.1
作者：
Bertrand, JR;Pottier, M;Malvy, C
通讯作者：
Malvy, C
DOI：
10.1124/jpet.105.100347
发表时间：
2006-05-01
影响因子：
3.5
作者：
Cheng, K;Ye, ZY;Mahato, RI
通讯作者：
Mahato, RI
影响因子：
2.7
作者：
Braasch, DA;Paroo, Z;Corey, DR
通讯作者：
Corey, DR
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R