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However, current small molecule\u2010regulated synthetic gene switches face clinical limitations such as long\u2010term side effects and metabolic disturbances. Here, we develop a natural sweetener\n                    <jats:styled-content>p<\/jats:styled-content>\n                    sicose\u2010ind\n                    <jats:styled-content>u<\/jats:styled-content>\n                    cible t\n                    <jats:styled-content>r<\/jats:styled-content>\n                    ansgene\n                    <jats:styled-content>e<\/jats:styled-content>\n                    xpression (PURE) system based on the transcriptional repressor PsiR from\n                    <jats:italic>Agrobacterium tumefaciens<\/jats:italic>\n                    . We increase the induction sensitivity of PURE using computational docking to identify candidate PsiR mutations (PsiR\n                    <jats:sub>T135N;V134S<\/jats:sub>\n                    ), thereby enhancing reporter expression in cell cultures exposed to low psicose concentrations. As a proof\u2010of\u2010concept, the designer cells equipped with the PURE system are encapsulated and implanted into the peritoneal cavity of type 1 diabetic (T1D) mice or high\u2010fat diet (HFD)\u2010induced obesity model mice. We show\u00a0that the designer cells could regulate insulin expression to effectively lower blood glucose levels in T1D model mice and induce an anti\u2010obesity therapeutic protein (thymic stromal lymphopoietin, mTSLP) to reduce body weight in HFD mice, when the psicose\u2010containing soft drink (psicose cola) is orally administered. This study provides a practical and user\u2010friendly approach for sustained therapeutic protein delivery in next\u2010generation cell\u2010based therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514226","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:43:26Z","timestamp":1767591806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Natural Sweetener\u2010inducible Genetic Switch Controls Therapeutic Protein Expression in Mammals"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-1040","authenticated-orcid":false,"given":"Longliang","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Breast Surgery School of Medicine Tongji Hospital Tongji University  Shanghai 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University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingwan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Biomedical Synthetic Biology Research Center Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoding","family":"Ma","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center 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