Inhibition of genes expression of SARS coronavirus by synthetic small interfering RNAs.

Inhibition of genes expression of SARS coronavirus by synthetic small interfering RNAs.
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通过合成小干扰RNA抑制SARS冠状病毒基因表达。

DOI:
10.1038/sj.cr.7290286
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发表时间:
2005-03
期刊:
影响因子:
44.1
通讯作者:
Jin YX
Jin YX
中科院分区:
生物学1区
文献类型:
--
作者:
Shi Y;Yang DH;Xiong J;Jia J;Huang B;Jin YX

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RNA干扰(RNAi)由双链RNA(dsRNA)的存在触发,并通过特异性降解含有相同序列的mRNA导致同源基因表达的沉默。dsRNA介导的RNAi可用于多种真核生物中以诱导基因表达的序列特异性抑制。近年来,人工合成的21-23个核苷酸(nt)的3′端突出的小干扰RNA(siRNA)被发现能介导哺乳动物细胞中有效的序列特异性mRNA降解。在这里,我们研究了针对SARS冠状病毒结构蛋白E,M和N的合成siRNA双链体在细胞培养系统中的作用。在26个siRNA双链体中,我们获得了3个siRNA双链体,其在Vero E6细胞中在60 nM的浓度下可以序列特异性地降低靶基因的表达超过80%。在0 ~ 60 nM范围内,下调效果与siRNA双链体的浓度相关。我们的结果还表明,许多无活性的siRNA双链体可以通过简单地将反义链的5'端解配对而获得生命。结果表明,siRNA能够抑制SARS冠状病毒基因的表达,可能成为SARS治疗的新策略。
RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequence. dsRNA-mediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression. Synthetic 21-23 nucleotide (nt) small interfering RNA (siRNA) with 2 nt 3′ overhangs was recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we studied the effects of synthetic siRNA duplexes targeted to SARS coronavirus structural proteins E, M, and N in a cell culture system. Among total 26 siRNA duplexes, we obtained 3 siRNA duplexes which could sequence-specifically reduce target genes expression over 80% at the concentration of 60 nM in Vero E6 cells. The downregulation effect was in correlation with the concentrations of the siRNA duplexes in a range of 0∼60 nM. Our results also showed that many inactive siRNA duplexes may be brought to life simply by unpairing the 5' end of the antisense strands. Results suggest that siRNA is capable of inhibiting SARS coronavirus genes expression and thus may be a new therapeutic strategy for treatment of SARS.
DOI: 10.1093/emboj/20.23.6877
发表时间: 2001-12-03
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
Elbashir, SM;Martinez, J;Tuschl, T
通讯作者: Tuschl, T
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发表时间: 2002-09-01
影响因子: 5.4
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发表时间: 2003-05-24
期刊: Lancet (London, England)
影响因子: --
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DOI: 10.1099/vir.0.19505-0
发表时间: 2003-12-01
影响因子: 3.8
作者:
Ng, ML;Tan, SH;Ling, AE
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