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2'-O-甲基化修饰的反 MDR1 siRNA 双链中部错配的沉默活性。

Silencing activity of 2'-O-methyl modified anti-MDR1 siRNAs with mismatches in the central part of the duplexes.

机构信息

Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.

出版信息

FEBS Lett. 2011 Jul 21;585(14):2352-6. doi: 10.1016/j.febslet.2011.06.003. Epub 2011 Jun 23.

Abstract

The thermodynamic properties of siRNA duplexes are important for their silencing activity. siRNAs with high thermodynamic stability of both the central part of the duplex and in the whole, usually display low silencing activity. Destabilization of the central part of the siRNA duplex could increase its silencing activity. However, mismatches located in the central part of the duplex could substantially decrease the amount of RNAi efficacy, hindering active RISC formation and function. In this study, we examined the impact of duplex destabilization by nucleotide substitutions in the central part (7-10 nt counting from the 5'-end of the antisense strand) of the nuclease-resistant siRNA on its silencing activity.

摘要

siRNA 双链体的热力学性质对其沉默活性很重要。双链体中心部分和整体热力学稳定性高的 siRNA,通常显示出低的沉默活性。siRNA 双链体中心部分的去稳定化可以提高其沉默活性。然而,位于双链体中心部分的错配会显著降低 RNAi 的效果,阻碍活性 RISC 的形成和功能。在这项研究中,我们研究了在(从反义链 5'端开始数第 7-10 个核苷酸)耐核酸酶 siRNA 的双链体中心部分的核苷酸取代对其沉默活性的影响。

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