干扰RNA的非靶免疫副作用及其siRNA序列设计与化学修饰  

Off-target Effects of RNAi and Design of Highly Effective Modified siRNAs

作　　者：韩秋菊[1] 张彩[1] 张建[1] 田志刚[1,2] 

机构地区：[1]山东大学药学院免疫药理与免疫治疗研究所 [2]中国科学技术大学免疫学研究所,合肥230027

出　　处：《生物化学与生物物理进展》2007年第4期343-347,共5页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展计划(973)项目(2004CB518807和2006CB504300)~~

摘　　要：siRNA介导的RNA干扰技术已经成为基因功能研究和开展疾病治疗的有用工具.近年发现,siRNA在哺乳动物体内可激活天然免疫系统,诱导干扰素等炎症因子的分泌,并且可非特异性抑制某些非靶基因的表达,有可能极大限制RNA干扰技术的应用.进行高效特异性siRNA的设计和修饰,以保持或者增强siRNA的特异性靶基因沉默作用,又消除siRNA对机体的非靶免疫副作用,成为使siRNA安全有效应用于临床治疗的关键.RNA interference mediated by short interfering RNA is widely used to study functional genes and also being developed for therapeutic applications. However, recent study demonstrated that siRNA might activate innate immune system and induce huge production of inflammatory cytokines in mammals, and also randomly inhibit expression of undesired genes. Designing highly effective siRNAs or modifying the siRNA to retain or enhance the silence efficiency and meanwhile abolish the off-target effects associated with immunostimulation then become the key techniques in application of siRNAs as safe and effective therapeutic agents.

关 键 词：RNA干扰 SIRNA TLR 非靶效应 

分 类 号：Q503[生物学—生物化学]