Orthogonal Activation of RNA‐Cleaving DNAzymes in Live Cells by Reactive Oxygen Species

• Published in: Angewandte Chemie International Edition Vol. 58; no. 40; pp. 14167 - 14172
• Main Authors: Xiao, Lu, Gu, Chunmei, Xiang, Yu
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-10-2019
• Edition: International ed. in English
• Subjects: Activation; Aging; DNAzyme; fluorescence; Gene expression; Gene regulation; Hydrogen peroxide; Immune system; Organic chemistry; Oxidative stress; phenylboronate; Phosphorothioate; Reactive oxygen species; Ribonucleic acid; RNA; Zinc; DNAzyme; phenylboronate; fluorescence; phosphorothioate; reactive oxygen species
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201908105

RNA‐cleaving DNAzymes are useful tools for intracellular metal‐ion sensing and gene regulation. Incorporating stimuli‐responsive modifications into these DNAzymes enables their activities to be spatiotemporally and chemically controlled for more precise applications. Despite the successful development of many caged DNAzymes for light‐induced activation, DNAzymes that can be intracellularly activated by chemical inputs of biological importance, such as reactive oxygen species (ROS), are still scarce. ROS like hydrogen peroxide (H2O2) and hypochlorite (HClO) are critical mediators of oxidative stress‐related cell signaling and dysregulation including activation of immune system as well as progression of diseases and aging. Herein, we report ROS‐activable DNAzymes by introducing phenylboronate and phosphorothioate modifications to the Zn2+‐dependent 8–17 DNAzyme. These ROS‐activable DNAzymes were orthogonally activated by H2O2 and HClO inside live human and mouse cells.
RNA‐cleaving DNAzymes containing H2O2‐responsive and HClO‐responsive modifications are orthogonally activated by these two reactive oxygen species (ROS) inside live cells. This enables precise intracellular activation of DNAzymes under oxidative stress to study ROS‐related biological process.