Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference
Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference
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DOI：
10.1093/nar/gkf627
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发表时间：
2002-11-15
影响因子：
14.9
通讯作者：
Takaku, H
中科院分区：
文献类型：
--
作者：
Park, WS;Miyano-Kurosaki, N;Takaku, H
RNA干扰（RNAi）现象是最近观察到的过程，其中将双链RNA（dsRNA）引入细胞中导致含有相同序列的mRNA的特异性降解。通过RNA酶III切割较长dsRNA产生的21-23 nt指导RNA与序列特异性mRNA降解相关。在这里，我们发现dsRNA特异性抑制HIV-1基因的表达。为了研究dsRNA介导的HIV-1感染细胞中的基因干扰，我们设计了六个含有HIV-1 gag和env基因的长dsRNA。在HIV-1感染的细胞中，HIV-1复制被dsRNA以序列特异性方式完全抑制。特别是含有HIV-1 env基因的gp 120的主要CD 4结合结构域序列的E2 dsRNA，在相对长的时间内显著抑制PBMC中HIV-1 p24抗原的表达。双链RNA干扰技术有望成为抗HIV-1基因治疗的新策略。
The RNA interference (RNAi) phenomenon is a recently observed process in which the introduction of a double-stranded RNA (dsRNA) into a cell causes the specific degradation of a mRNA containing the same sequence. The 21-23 nt guide RNAs, generated by RNase III cleavage from longer dsRNAs, are associated with sequence-specific mRNA degradation. Here, we show that dsRNA specifically suppresses the expression of HIV-1 genes. To study dsRNA-mediated gene interference in HIV-1-infected cells, we have designed six long dsRNAs containing the HIV-1 gag and env genes. HIV-1 replication was totally suppressed in a sequence-specific manner by the dsRNAs in HIV-1-infected cells. Especially, E2 dsRNA containing the major CD4-binding domain sequence of gp120, as the target of the HIV-1 env gene, dramatically inhibited the expression of the HIV-1 p24 antigen in PBMCs for a relatively long time. The dsRNA interference method seems to be a promising new strategy for anti-HIV-1 gene therapeutics.