Enhanced gene silencing by the application of multiple specific small interfering RNAs

Enhanced gene silencing by the application of multiple specific small interfering RNAs
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DOI:
10.1016/s0014-5793(03)00893-7
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发表时间:
2003-09-25
期刊:
影响因子:
3.5
通讯作者:
Erb, P
Erb, P
中科院分区:
生物学3区
文献类型:
--
作者:
Ji, JM;Wernli, M;Erb, P

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小干扰RNA双链体(siRNA)在各种真核细胞中诱导基因沉默,尽管通常是以不完全的方式。使用化学合成的siRNA靶向HIV-1共受体CXCR 4或诱导凋亡的Fas配体(FasL),共转染细胞与两个或更多个siRNA双链体靶向相同mRNA上的不同位点,导致增强的基因沉默相比,每个单一的siRNA。这表现在蛋白质和mRNA表达的下调,以及功能上抑制CXCR 4介导的HIV感染和FasL介导的细胞凋亡。确定的FasL特异性siRNA的转染效率是剂量依赖性的,并且在测试的siRNA之间变化,但不是增强的基因沉默的主要原因。(C)2003年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
Small interfering RNA duplexes (siRNA) induce gene silencing in various eukaryotic cells, although usually in an incomplete manner. Using chemically synthesized siRNAs targeting the HIV-1 co-receptor CXCR4 or the apoptosis-inducing Fas-ligand (FasL), co-transfection of cells with two or more siRNA duplexes targeting different sites on the same mRNA resulted in an enhanced gene silencing compared with each single siRNA. This was shown in the down-regulation of protein and mRNA expression, and functionally in the inhibition of CXCR4-mediated HIV infection and of FasL-mediated cell apoptosis. Transfection efficiency determined for the FasL-specific siRNAs was dose-dependent and varied among the siRNAs tested, but was not the main reason for the enhanced gene silencing. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.