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Herein, we engineer an activatable bispecific aptamer switch, termed the Allosteric RNA G\u2010quadruplex ON\u2010switch (ARGON), which integrates an rG4\u2010targeting L\u2010RNA Apt.4\u20101c module (masked by a glutathione (GSH)\u2010cleavable lock strand) with a tumor receptor\u2010targeting Sgc8 DNA aptamer to precisely target rG4s and regulate downstream cellular activities within tumor cells. The AND logic\u2010gated ARGON is activated exclusively in tumor cells that exhibit both tumor receptor overexpression and elevated GSH levels. Following cellular uptake, GSH\u2010triggered lock cleavage exposes L\u2010Apt.4\u20101c's rG4\u2010binding domain, enabling binding oncogenic\n                    <jats:italic>Bcl2<\/jats:italic>\n                    rG4. Then activated ARGON regulates rG4\u2010associated tumor cellular functions while sparing normal cells. Besides, we apply ARGON to target human telomerase RNA component (\n                    <jats:italic>hTERC<\/jats:italic>\n                    ) rG4 to show our method's generality. Collectively, by integrating cell\u2010surface addressing with intracellular environmental sensing, our work reports an \u201cold\u2010chemistry\u2010new\u2010trick\u201d framework for regulating nucleic acid structures, enabling conditional targeting of cellular RNA structures with minimal off\u2010target effects and propelling aptamer\u2010based precision biomedicine forward.\n                  <\/jats:p>","DOI":"10.1002\/anie.4594145","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:49:21Z","timestamp":1778683761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AND\u2010Logic\u2010Gated Aptamer Switch for Precise Targeting and Regulation of RNA G\u2010Quadruplexes"],"prefix":"10.1002","volume":"65","author":[{"given":"Dan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry and State Key Laboratory of Marine Environmental Health City 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