在 siRNA 种子区选择化学修饰可以抑制脱靶效应。

Selection of Chemical Modifications in the siRNA Seed Region That Repress Off-Target Effect.

机构信息

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.

Center for Quantum Life Sciences and Department of Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan.

出版信息

Methods Mol Biol. 2021;2282:17-30. doi: 10.1007/978-1-0716-1298-9_2.

DOI:10.1007/978-1-0716-1298-9_2

PMID:33928567

Abstract

RNA interference mediated by small interfering RNA (siRNA) has been widely used as a procedure to knock down the expression of an intended target gene with perfect sequence complementarity. However, siRNA often exhibits off-target effects on genes with partial sequence complementarities. Such off-target effect is an undesirable adverse effect for knocking down a target gene specifically. Here we describe the powerful strategy to avoid off-target effects without affecting the RNAi activity by the introduction of DNA or 2'-O-methyl modifications in the siRNA seed region. These two types of chemical modifications repress off-target effects through different molecular mechanisms.

摘要

小干扰 RNA (siRNA)介导的 RNA 干扰已被广泛用作一种通过与靶基因完全互补的序列来降低靶基因表达的方法。然而，siRNA 通常会对部分序列互补的基因产生脱靶效应。这种脱靶效应是特异性降低靶基因表达的一种不理想的不良反应。在这里，我们描述了一种通过在 siRNA 种子区引入 DNA 或 2'-O-甲基修饰来避免脱靶效应而不影响 RNAi 活性的强大策略。这两种类型的化学修饰通过不同的分子机制抑制脱靶效应。