Combinatorially Inducible RNA Interference Triggered by Chemically Modified Oligonucleotides
Combinatorially Inducible RNA Interference Triggered by Chemically Modified Oligonucleotides
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DOI：
10.1021/ja1107436
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发表时间：
2011-03-02
影响因子：
15
通讯作者：
Yokobayashi, Yohei
中科院分区：
文献类型：
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作者：
Kumar, Deepak;Kim, Sang Hoon;Yokobayashi, Yohei
化学诱导的RNA干扰（RNAi）能够对几乎任何基因进行时间和/或空间控制，使其可用于基因功能的研究。发现潜在的药物靶点和基因治疗应用。在这里，我们描述了一种新的诱导型RNAi平台，其中正交化学修饰的寡核苷酸用于以组合方式触发两个基因的沉默。我们开发了一种模块化RNA架构，由寡核苷酸传感器茎环和RNAi效应结构域组成，其被设计为在添加寡核苷酸诱导剂后发生结构转变。诱导的结构变化允许RNA被RNAi机制加工，最终导致由RNAi效应子模块编码的靶标的基因沉默。多基因的组合调控将加速复杂基因间相互作用的研究和新药靶点的筛选。
Chemically inducible RNA interference (RNAi) enables temporal and/or spatial control of virtually any gene, making it useful for study of gene functions., discovery of potential drug targets, and gene therapy applications. Here we describe a new inducible RNAi platform in which orthogonal chemically modified oligonucleotides are used to trigger silencing of two genes in a combinatorial manner. We developed a modular RNA architecture consisting of an oligonucleotide sensor stem-loop and an RNAi effector domain, that is designed to undergo a structural shift upon addition of an oligonucleotide inducer. The induced structural change allows the RNA to be processed by the RNAi machinery, ultimately resulting in gene silencing of the target encoded by the RNAi effector module. Combinatorial regulation of multiple genes should accelerate studies of complex gene-gene interactions and screening of new drug targets.