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干扰RNA的非靶免疫副作用及其siRNA序列设计与化学修饰 被引量：3

Off-target Effects of RNAi and Design of Highly Effective Modified siRNAs
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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.
作者 韩秋菊 张彩 张建 田志刚
机构地区 山东大学药学院免疫药理与免疫治疗研究所 中国科学技术大学免疫学研究所
出处 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 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)~~
关键词 RNA干扰 SIRNA TLR 非靶效应 RNAi, siRNA, TLR, off-target effect
分类号 Q503 [生物学—生物化学]
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参考文献30

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同被引文献40

  • 1魏海明,邬鹏,田志刚.NK细胞识别的新模式——压力诱导模式[J].中国肿瘤生物治疗杂志,2005,12(2):85-88. 被引量：5
  • 2刘晓东,张增艳,姚乌兰,辛志勇.在小麦上实施大麦条斑病毒诱导的基因沉默[J].作物学报,2005,31(11):1518-1520. 被引量：5
  • 3洪德峰,牛吉山,张丽娜,王映红,任江萍.小麦TaEDR1基因dsRNAi表达载体的构建及遗传转化[J].生物技术通报,2006,22(C00):264-267. 被引量：4
  • 4康国章,官春云,肖向红,郭天财,朱云集,刘锋.小麦淀粉合酶基因Ⅲ片段的克隆及反义和RNA干扰载体的构建[J].中国生物工程杂志,2007,27(8):40-45. 被引量：6
  • 5Jiang W, Sun R, Wei H, Tian Z. Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages. Proc Natl Acad Sci USA, 2005, 102 (47): 17077-17082.
  • 6Radaeva S, Sun R, Jaruga B, et al. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor apoptosis-inducing ligand-dependent necrosis factor-related manners. Gastroenterology,2006, 1311 (2): 435-452.
  • 7Chen Y, Sun R, Jiang W, et al. Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK celland IFN-gamma-dependent manner. J Hepatol, 2007, 47(2): 183-190.
  • 8Zhang J, Sun R, Wei H, et al. Toll-like receptor 3 agonist enhances IFN-gamma and TNF-alpha production by murine uterine NK cells. Int Immunopharmacol, 2007, 7 (5): 588-596.
  • 9Zhang J, Wei H, Wu D, Tian Z. Toll-like receptor 3 agonist induces impairment of uterine vascular remodeling and fetal losses in CBAxDBA/2 mice. J Reprod Immunol, 2007,74 (1-2): 61-67.
  • 10Zhou R, Wei H, Sun R, et al. NKG2D recognition mediates Toll-like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice. Proc Natl Acad Sci USA, 2007, 104 (18): 7512-7515.

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生物化学与生物物理进展
2007年 第4期

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