siRNA与固有免疫

siRNA and Innate Immunity

转染小干扰RNA片段(small interfering RNA,siRNA)被广泛用于沉默基因表达.外源性核酸短链的进入能激活Toll样受体,触发免疫应答,促进机体炎症因子的表达与释放.siRNA还能活化双链RNA依赖性蛋白激酶(dsRNA-dependent protein kinase,PKR)等胞内模式识别受体,通过免疫反应引起机体功能障碍.siRNA的免疫效应与其核苷酸链的长短、碱基序列、核糖结构等密切相关,相应的化学修饰能阻断其激活模式识别受体,抑制固有免疫应答.本文综述了近年来siRNA对固有免疫应答的分子机制,为改善基因沉默效应和拓展该技术的临床应用提供有益帮助.

RNA interference mediated by small interfering RNA （siRNA） is a widely applied biotechnique to select silence genes in vitro and in vivo. However, the exogenous introduced siRNA is a potent activator of the innate immune system via a Toll-like receptor （TLR） pathway, which increases the expression and release of inflammatory cytokines. Furthermore, siRNA also can activate cytosolic RNA- binding proteins such as PKR, which is associated with cellular dysfunction and injury through inflammation. The induction of immune system by siRNA is dependent on certain molecular features such as the length of siRNA, the base sequences and the structure of ribose. Thus, specific chemical modification of siRNA is an effective method to abrogate the recognition of pattern-recognition receptors （PRRs） and suppress non-specific immune response. In this review, we discussed recent advances regarding the mechanisms underlying innate immune activation by siRNA, which would helpful to improve the gene-silencing function and to expand the clinical applications of this technology.