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Hydrogen peroxide-triggered gene silencing in mammalian cells through boronated antisense oligonucleotides

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Abstract

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) involved in various diseases, including neurodegeneration, diabetes, and cancer. Here, we introduce a new approach to use H2O2 to modulate specific gene expression in mammalian cells. H2O2-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 (dTB), 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 H2O2 addition. Furthermore, we demonstrated H2O2-triggered gene silencing in mammalian cells using antisense oligonucleotides (ASOs) modified with dTB. 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.

Graphical abstract: Hydrogen peroxide-triggered gene silencing in mammalian cells through boronated antisense oligonucleotides

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Publication details

The article was received on 05 Oct 2017, accepted on 21 Nov 2017 and first published on 06 Dec 2017


Article type: Edge Article
DOI: 10.1039/C7SC04318J
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY license
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    Hydrogen peroxide-triggered gene silencing in mammalian cells through boronated antisense oligonucleotides

    S. Mori, K. Morihiro, T. Okuda, Y. Kasahara and S. Obika, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C7SC04318J

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