siRNA核糖分子化学修饰对RNAi功能的影响

Effects of Chemically-Modified Ribose in siRNA on RNA Interference

RNA干扰(RNAi)是基于正常RNA生理调节反应,主要由小干扰RNA(siRNA)引发的转录后基因沉默现象。RNAi技术是基因功能研究的重要手段。目前困扰siRNA进入临床的主要困难有siRNA分子易降解、稳定性差、转运效率低、存在靶外效应和免疫刺激反应等。siRNA分子骨架中核糖化学修饰能够一定程度克服上述障碍,降低siRNA给药剂量,减少副作用,是siRNA进入临床最可能的方式。对核糖分子常用位点尤其是2-′羟基化学修饰后siRNA分子的药动学性状及RNAi功能做了分析。

RNA Interference （RNAi） has been recognized as a powerful tool to regulate gene function and has been used for sequence-specific, post-transcriptional gene silencing by knocking down mRNA in mammalian cells. The potential use of small interfering RNA （siRNA） as therapeutic agents has attracted great attention as a novel approaeh for treating severe and chronic disease. However, the relatively high dose of siRNA required for gene silencing due to its instability, nuclease easily degradation and difficulty in delivery limits its therapeutic applications. This review discussed a ribose chemically-modified strategy to improve therapeutie efficacy as well as to abrogate off-target effects and immunostimulation caused by siRNAs. These kinds of design in siRNA molecules has successfully improved their physicoehemical and pharmaceutical properties and shown great expectation to overcome the barriers to RNAi-based therapies.