Issue 5, 2018

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
05 okt 2017
Accepted
21 nov 2017
First published
06 dec 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 1112-1118

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, 9, 1112 DOI: 10.1039/C7SC04318J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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