Gene silencing through RNA interference (RNAi) in vivo: Strategies based on the direct application of siRNAs
Gene silencing through RNA interference (RNAi) in vivo: Strategies based on the direct application of siRNAs
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DOI：
10.1016/j.jbiotec.2005.12.003
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发表时间：
2006-06-25
影响因子：
4.1
通讯作者：
Aigner, A
中科院分区：
文献类型：
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作者：
Aigner, A
RNA干扰（RNAi）不仅为体外靶点验证提供了巨大的潜力，而且作为基于靶基因的高度特异性和有效沉默的新型治疗策略，例如在肿瘤治疗中。由于它依赖于小干扰RNA（siRNA），其是RNAi诱导的特异性mRNA降解的介质，因此主要问题是将治疗活性siRNA递送到体内靶组织/靶细胞中。出于安全性原因，基于（病毒）载体递送的策略可能仅具有有限的临床用途。更理想的方法是直接应用具有催化活性的siRNA。这篇综述强调了最近的知识的指导方针选择的siRNA显示高活性的情况下，非特异性siRNA的影响。然后重点介绍了直接在体内使用siRNA分子的方法，并对基于直接应用siRNA诱导RNAi的体内研究进行了全面概述。一种有前景的方法是通过化学未修饰的siRNA与聚乙烯亚胺（PEI）的复合物的体内siRNA递送。描述了基于PEI/siRNA靶向肿瘤相关基因的体内抗肿瘤作用。(c)2005 Elsevier B. V.保留所有权利。
RNA interference (RNAi) offers great potential not only for in vitro target validation, but also as a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene, e.g. in tumor therapy. Since it relies on small interfering RNAs (siRNAs), which are the mediators of RNAi-induced specific mRNA degradation, a major issue is the delivery of therapeutically active siRNAs into the target tissue/target cells in vivo. For safety reasons, strategies based on (viral) vector delivery may be of only limited clinical use. The more desirable approach is to directly apply catalytically active siRNAs. This review highlights the recent knowledge on the guidelines for the selection of siRNAs which show high activity in the absence of non-specific siRNA effects. It then focuses on approaches to directly use siRNA molecules in vivo and gives a comprehensive overview of in vivo studies based on the direct application of siRNAs to induce RNAi. One promising approach is the in vivo siRNA delivery through complexation of chemically unmodified siRNAs with polyethylenimine (PEI). The anti-tumoral effects of PEI/siRNA-based targeting of tumor-relevant genes in vivo are described. (c) 2005 Elsevier B.V. All rights reserved.