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小干扰RNA的化学修饰

Chemical modification of siRNA.

作者信息

Chernolovskaya Elena L, Zenkova Marina A

机构信息

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk, 630090, Russian Federation.

出版信息

Curr Opin Mol Ther. 2010 Apr;12(2):158-67.

Abstract

siRNAs are widely used for the control of gene expression in molecular biology and experimental pharmacology. siRNA molecules are the most efficient and specific inhibitors of gene expression to have been discovered, acting at nanomolar and subnanomolar concentrations. Challenges associated with nuclease stability, selecting effective sequences, reducing off-target effects and achieving efficient delivery to target cells and tissues have significantly limited the biomedical applications of siRNA. However, chemical modification is a powerful tool for improving the properties of siRNA. This review examines recent data regarding chemical modifications used to develop potent effectors of gene silencing. The correlation between thermal stability and potency, and between nuclease resistance and duration of the silencing effect, are discussed with relation to chemically modified siRNAs.

摘要

小干扰RNA(siRNAs)在分子生物学和实验药理学中被广泛用于控制基因表达。siRNA分子是已发现的最有效、最具特异性的基因表达抑制剂,在纳摩尔和亚纳摩尔浓度下起作用。与核酸酶稳定性、选择有效序列、减少脱靶效应以及实现向靶细胞和组织的有效递送相关的挑战显著限制了siRNA的生物医学应用。然而,化学修饰是改善siRNA性质的有力工具。本综述研究了有关用于开发强效基因沉默效应物的化学修饰的最新数据。结合化学修饰的siRNAs,讨论了热稳定性与效力之间以及核酸酶抗性与沉默效应持续时间之间的相关性。

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