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

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 (dT ), 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 dT . 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.