Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.
Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.
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DOI：
10.1016/j.addr.2016.03.005
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发表时间：
2016-08-01
影响因子：
16.1
通讯作者：
Shankar P
中科院分区：
文献类型：
--
作者：
Swamy MN;Wu H;Shankar P
RNA干扰（RNA interference，RNAi）是一种有效的基因沉默技术，已被广泛应用于抑制HIV-1复制过程中的CCR 5和病毒基因等宿主因子。较新的基于核酸酶的基因编辑技术，如锌指核酸酶（ZFN）、转录激活因子样效应物核酸酶（TALEN）和成簇规则间隔短回文重复序列（CRISPR）/Cas9系统，也为消除特定基因提供了强大的工具。由于共受体使用的差异和HIV-1基因组的高度可变性，需要抑制宿主因子和病毒基因的组合以有效预防和治疗HIV-1感染。尽管RNAi有效需要小干扰/短发夹RNA（si/shRNA）介体的持续存在，但基因编辑系统中核酸酶的持续表达是不期望的。因此，RNAi提供了在感染和未感染细胞中表达多种沉默子的唯一实用方法，这是有效预防/治疗感染所需的。RNAi领域在si/shRNA设计、靶向递送至HIV-1易感细胞以及在临床前人源化小鼠模型中测试功效方面已经取得了若干进展。本文就RNAi技术在HIV-1预防和治疗方面的最新进展作一综述。
RNA interference (RNAi) provides a powerful tool to silence specific gene expression and has been widely used to suppress host factors such as CCR5 and/or viral genes involved in HIV-1 replication. Newer nuclease-based gene-editing technologies, such as zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, also provide powerful tools to ablate specific genes. Because of differences in co-receptor usage and the high mutability of the HIV-1 genome, a combination of host factors and viral genes needs to be suppressed for effective prevention and treatment of HIV-1 infection. Whereas the continued presence of small interfering/short hairpin RNA (si/shRNA) mediators is needed for RNAi to be effective, the continued expression of nucleases in the gene-editing systems is undesirable. Thus, RNAi provides the only practical way for expression of multiple silencers in infected and uninfected cells, which is needed for effective prevention/treatment of infection. There have been several advances in the RNAi field in terms of si/shRNA design, targeted delivery to HIV-1 susceptible cells, and testing for efficacy in preclinical humanized mouse models. Here, we comprehensively review the latest advances in RNAi technology towards prevention and treatment of HIV-1.
影响因子：
14.9
作者：
Li, Zhen;Fortin, Yves;Shen, Shi-Hsiang
通讯作者：
Shen, Shi-Hsiang