Lee Nan Sook, Rossi John J
Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Virus Res. 2004 Jun 1;102(1):53-8. doi: 10.1016/j.virusres.2004.01.015.
Small interfering RNAs (siRNAs) have been shown to direct sequence-specific inhibition of gene expression in mammalian cells. siRNAs are RNA duplexes of 21-23 nucleotides (nts) with approximately 2nt 3' overhangs that can induce degradation of their homologous target mRNAs without interferon responses in mammalian cells. The degradation of the target occurs at the post-transcriptional level, meaning a post-transcriptional gene silencing (PTGS) mechanism called as RNA interference (RNAi). RNAi has emerged as an efficient method to inhibit gene expression in mammalian cells with increasingly successful cases of knockdown of many specific genes. Recent works have shown that the use of RNAi could inhibit HIV-1 replication by targeting viral or cellular genes. RNAi can be considered as a gene-specific therapeutic option for controlling HIV-1 replication. However, the control of HIV-1 replication has become complex because of the limited effectiveness of existing anti-HIV-1 agents and the high speed mutation rate of the HIV-1 genome. Careful assessments are required for the potential of RNAi as a gene therapy approach for controlling HIV-1 replication. This review will discuss the status of the science using RNAi for controlling HIV-1 replication and will describe possible problems for therapeutic applications of RNAi-mediated technologies for HIV-1 behind this novel mechanism.
小干扰RNA（siRNA）已被证明可在哺乳动物细胞中引导基因表达的序列特异性抑制。siRNA是21-23个核苷酸（nt）的RNA双链体，带有约2nt的3'突出端，可在哺乳动物细胞中诱导其同源靶mRNA的降解而不引发干扰素反应。靶标的降解发生在转录后水平，即一种称为RNA干扰（RNAi）的转录后基因沉默（PTGS）机制。随着许多特定基因敲低的成功案例越来越多，RNAi已成为抑制哺乳动物细胞中基因表达的有效方法。最近的研究表明，使用RNAi可通过靶向病毒或细胞基因来抑制HIV-1复制。RNAi可被视为控制HIV-1复制的基因特异性治疗选择。然而，由于现有抗HIV-1药物的有效性有限以及HIV-1基因组的高突变率，HIV-1复制的控制变得复杂。需要对RNAi作为控制HIV-1复制的基因治疗方法的潜力进行仔细评估。本综述将讨论使用RNAi控制HIV-1复制的科学现状，并将描述这种新机制背后RNAi介导技术在HIV-1治疗应用中可能存在的问题。
