Volume 131, Issue 40 pp. 14305-14310
Zuschrift

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

Lu Xiao

Lu Xiao

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus, Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084 China

These authors contributed equally to this work.

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Chunmei Gu

Chunmei Gu

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus, Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084 China

These authors contributed equally to this work.

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Assoc. Prof. Yu Xiang

Corresponding Author

Assoc. Prof. Yu Xiang

Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus, Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084 China

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First published: 17 July 2019
Citations: 17

Abstract

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.

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