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Designing highly active siRNAs for therapeutic applications

dr.qinan 添加于 2011-1-11 12:33 | 1397 次阅读 | 0 个评论

作者
Walton SP, Wu M, Gredell JA, Chan C
摘要
The discovery of RNA interference (RNAi) generated considerable interest in developing short interfering RNAs (siRNAs) for understanding basic biology and as the active agents in a new variety of therapeutics. Early studies showed that selecting an active siRNA was not as straightforward as simply picking a sequence on the target mRNA and synthesizing the siRNA complementary to that sequence. As interest in applying RNAi has increased, the methods for identifying active siRNA sequences have evolved from focusing on the simplicity of synthesis and purification, to identifying preferred target sequences and secondary structures, to predicting the thermodynamic stability of the siRNA. As more specific details of the RNAi mechanism have been defined, these have been incorporated into more complex siRNA selection algorithms, increasing the reliability of selecting active siRNAs against a single target. Ultimately, design of the best siRNA therapeutics will require design of the siRNA itself, in addition to design of the vehicle and other components necessary for it to function in vivo. In this minireview, we summarize the evolution of siRNA selection techniques with a particular focus on one issue of current importance to the field, how best to identify those siRNA sequences likely to have high activity. Approaches to designing active siRNAs through chemical and structural modifications will also be highlighted. As the understanding of how to control the activity and specificity of siRNAs improves, the potential utility of siRNAs as human therapeutics will concomitantly grow.
详细资料
- 文献种类:期刊
- 期刊名称: The FEBS Journal
- 期刊缩写: FEBS J
- 期卷页: 2010年第277卷第23期 4806-4813页
- 地址: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA. spwalton@egr.msu.edu
- ISBN: 1742-464X
- 备注:PMID:21078115
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