Gene silencing by 2′-O-methyldithiomethyl-modified siRNA, a prodrug-type siRNA responsive to reducing environment
Gene silencing by 2′-O-methyldithiomethyl-modified siRNA, a prodrug-type siRNA responsive to reducing environment
复制标题
2-O-甲基二硫甲基修饰的 siRNA（一种响应还原环境的前药型 siRNA）进行基因沉默
DOI：
10.1016/j.bmcl.2015.12.074
复制
发表时间：
2016
影响因子：
2.7
通讯作者：
Hidehito Urata
中科院分区：
文献类型：
--
作者：
Yosuke Ochi;Mieko Imai;Osamu Nakagawa;Junsuke Hayashi;Shun-ichi Wada;Hidehito Urata
已经合成了带有各种2′-修饰的RNA，以努力提高核酸酶抗性。然而，小干扰RNA（siRNA）的基因沉默活性已经被化学修饰降低或有时被完全抑制。我们之前开发了一种合成2′-O-甲基二硫甲基修饰的RNA的后合成方法，该方法可以在还原条件下转化为未修饰的RNA，并将其命名为还原环境依赖的未催化化学转化RNA（REDUCT RNA）。在此，评估了带有2′-O-甲基二硫甲基基团的REDUCT siRNA的基因沉默活性。无论修饰位点如何，REDUCT siRNA都比未修饰的siRNA显示出更有效的基因沉默。该结果表明，REDUCT siRNA在细胞内转化为未修饰的siRNA作为前药型siRNA。
RNAs bearing various 2′-modifications have been synthesized in an effort to improve nuclease resistance. However, the gene silencing activity of small interfering RNAs (siRNAs) has been decreased or sometimes completely suppressed by the chemical modifications. We previously developed a post-synthetic approach for the synthesis of 2′-O-methyldithiomethyl-modified RNA, which can be converted into unmodified RNA under reducing conditions, and named it Reducing-Environment-Dependent Uncatalyzed Chemical Transforming RNA (REDUCT RNA). Here, the gene silencing activity of REDUCT siRNA bearing 2′-O-methyldithiomethyl groups was evaluated. REDUCT siRNA showed more effective gene silencing than unmodified siRNA regardless of the modification site. This result suggests that REDUCT siRNA is converted into unmodified siRNA inside cells as a prodrug-type siRNA.