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 (H O ) 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 Zn -dependent 8-17 DNAzyme. These ROS-activable DNAzymes were orthogonally activated by H O and HClO inside live human and mouse cells.
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