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高效且系统的 RNAi 介导的单寡核苷酸化合物沉默。

Potent and systematic RNAi mediated silencing with single oligonucleotide compounds.

机构信息

RXi Pharmaceuticals Corporation, Gateway Life Sciences Park, Worcester, Massachusetts 01605, USA.

出版信息

RNA. 2011 Jun;17(6):1032-7. doi: 10.1261/rna.2399411. Epub 2011 Apr 14.

DOI:10.1261/rna.2399411
PMID:21493786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3096035/
Abstract

RNA interference (RNAi) has been established as an important tool for functional genomics studies and has great promise as a therapeutic intervention for human diseases. In mammalian cells, RNAi is conventionally induced by 19-27-bp RNA duplexes generated by hybridization of two complementary oligonucleotide strands (oligos). Here we describe a novel class of RNAi molecules composed of a single 25-28-nucleotide (nt) oligo. The oligo has a 16-nt mRNA targeting region, followed by an additional 8-10 nt to enable self-dimerization into a partially complementary duplex. Analysis of numerous diverse structures demonstrates that molecules composed of two short helices separated by a loop can efficiently enter and activate the RNA-induced silencing complex (RISC). This finding enables the design of highly effective single-oligo compounds for any mRNA target.

摘要

RNA 干扰 (RNAi) 已被确立为功能基因组学研究的重要工具，并有望成为治疗人类疾病的一种治疗干预手段。在哺乳动物细胞中，RNAi 通常通过由两条互补寡核苷酸链（寡核苷酸）杂交产生的 19-27 个碱基对的 RNA 双链体诱导。在这里，我们描述了一类由单个 25-28 个核苷酸 (nt) 的寡核苷酸组成的新型 RNAi 分子。该寡核苷酸具有 16 个 nt 的 mRNA 靶向区域，其后是另外 8-10 个 nt，以使其能够自我二聚化形成部分互补双链体。对许多不同结构的分析表明，由两个短螺旋体通过环隔开的分子可以有效地进入并激活 RNA 诱导的沉默复合物 (RISC)。这一发现使得设计针对任何 mRNA 靶标的高效单寡核苷酸化合物成为可能。

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