Mori Shohei, Morihiro Kunihiko, Okuda Takumi, Kasahara Yuuya, Obika Satoshi
Graduate School of Pharmaceutical Sciences , Osaka University , 1-6 Yamadaoka , Suita , Osaka 565-0871 , Japan . Email:
National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) , 7-6-8 Saito-Asagi , Ibaraki , Osaka 567-0085 , Japan.
Chem Sci. 2017 Dec 6;9(5):1112-1118. doi: 10.1039/c7sc04318j. eCollection 2018 Feb 7.
Hydrogen peroxide (HO) is a reactive oxygen species (ROS) involved in various diseases, including neurodegeneration, diabetes, and cancer. Here, we introduce a new approach to use HO to modulate specific gene expression in mammalian cells. HO-responsive nucleoside analogues, in which the Watson-Crick faces of the nucleobases are caged by arylboronate moieties, were synthesized. One of these analogues, boronated thymidine ( ), was incorporated into oligodeoxynucleotides (ODNs) using an automated DNA synthesizer. The hybridization ability of this boronated ODN to complementary RNA was clearly switched in the off-to-on direction upon HO addition. Furthermore, we demonstrated HO-triggered gene silencing in mammalian cells using antisense oligonucleotides (ASOs) modified with . Our approach can be used for the regulation of any gene of interest by the sequence design of boronated ASOs and will contribute to the development of targeted disease therapeutics.
过氧化氢（HO）是一种活性氧（ROS），参与包括神经退行性变、糖尿病和癌症在内的多种疾病。在此，我们介绍一种利用HO调节哺乳动物细胞中特定基因表达的新方法。合成了HO响应性核苷类似物，其中核苷酸碱基的沃森-克里克面被芳基硼酸部分封闭。使用自动DNA合成仪将这些类似物之一硼化胸腺嘧啶（ ）掺入寡脱氧核苷酸（ODN）中。加入HO后，这种硼化ODN与互补RNA的杂交能力明显从关闭状态切换到开启状态。此外，我们使用用 修饰的反义寡核苷酸（ASO）在哺乳动物细胞中证明了HO触发的基因沉默。我们的方法可通过硼化ASO的序列设计用于调控任何感兴趣的基因，并将有助于开发靶向疾病治疗方法。
