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A significant challenge is the regulation of cellular processes in response to gaseous signaling molecules such as hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S). To address this, we present the design of Gas signaling molecule\u2010Responsive Artificial DNAzyme\u2010based Switches (GRAS) to manipulate cellular functions via H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010sensitive synthetic DNAzymes. By incorporating stimuli\u2010responsive moieties to the phosphorothioate backbone, DNAzymes are strategically designed with H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010responsive azide groups at cofactor binding locations within the catalytic core region. These modifications enable their activation through H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010reducing decaging, thereby initiating substrate cleavage activity. Our approach allows for the flexible customization of various DNAzymes to regulate distinct cellular processes in diverse scenarios. Intracellularly, the enzymatic activity of GRAS promotes H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010induced cleavage of specific mRNA sequences, enabling targeted gene silencing and inducing apoptosis in cancer cells. Moreover, integrating GRAS with dynamic DNA assembly allows for grafting these functional switches onto cell surface receptors, facilitating H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010triggered receptor dimerization. This extracellular activation transmits signals intracellularly to regulate cellular behaviors such as migration and proliferation. Collectively, synthetic switches are capable of rewiring cellular functions in response to gaseous cues, offering a promising avenue for advanced targeted cellular engineering.\n                  <\/jats:p>","DOI":"10.1002\/anie.202410380","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T22:23:59Z","timestamp":1727389439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hydrogen Sulfide\u2010Triggered Artificial DNAzyme Switches for Precise Manipulation of Cellular Functions"],"prefix":"10.1002","volume":"63","author":[{"given":"Xuan","family":"Xie","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemo\/Biosensing and Chemometrics College of Chemistry and Chemical Engineering College of Biology Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology Hunan University  410082 Changsha P.\u2005R. 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