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To enable such therapeutic control, a mammalian gene switch is designed to be responsive to the natural sweetener xylose and its functionality is assessed in mouse studies. The gene switch consists of the bacterial transcription regulator XylR fused to a mammalian transactivator, which binds to an optimized promoter in the presence of xylose, thereby allowing dose\u2010dependent transgene expression. The sensitivity of SWEET (sweetener\u2010inducible expression of transgene) is improved by coexpressing a xylose transporter. Mice implanted with encapsulated SWEET\u2010engineered cells show increased blood levels of cargo protein when taking xylose\u2010sweetened water or coffee, or highly concentrated apple extract, while they do not respond to intake of a usual amount of carrots, which contain xylose. In a proof\u2010of\u2010concept therapeutic application study, type\u20101 diabetic mice engineered with insulin\u2010expressing SWEET show lowered glycemia and increased insulin levels when administered this fairly diabetic\u2010compliant sweetener, compared to untreated mice. A SWEET\u2010based therapy appears to have the potential to integrate seamlessly into patients\u2019 life\u2010style and food habits in the move toward personalized medicine.<\/jats:p>","DOI":"10.1002\/advs.202203193","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T22:45:55Z","timestamp":1667256355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Regulation of Transgene Expression by the Natural Sweetener Xylose"],"prefix":"10.1002","volume":"9","author":[{"given":"Silvia","family":"Galvan","sequence":"first","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Mattenstrasse 26 Basel CH\u20104058 Switzerland"}]},{"given":"Oliver","family":"Madderson","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Mattenstrasse 26 Basel CH\u20104058 Switzerland"}]},{"given":"Shuai","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Mattenstrasse 26 Basel CH\u20104058 Switzerland"}]},{"given":"Ana P.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Mattenstrasse 26 Basel CH\u20104058 Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-667X","authenticated-orcid":false,"given":"Martin","family":"Fussenegger","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering ETH Zurich  Mattenstrasse 26 Basel CH\u20104058 Switzerland"},{"name":"Faculty of Life Science University of Basel  Mattenstrasse 26 Basel CH\u20104058 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