{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:53:17Z","timestamp":1792633997217,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["785800"],"award-info":[{"award-number":["785800"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["27449.2 PFLS\u2010LS"],"award-info":[{"award-number":["27449.2 PFLS\u2010LS"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Body temperature is maintained at around 37 \u00b0C in humans, but may rise to 40 \u00b0C or more during high\u2010grade fever, which occurs in most adults who are seriously ill. However, endogenous temperature sensors, such as ion channels and heat\u2010shock promoters, are fully activated only at noxious temperatures above this range, making them unsuitable for medical applications. Here, a genetically encoded protein thermometer (human enhanced gene activation thermometer; HEAT) is designed that can trigger transgene expression in the range of 37\u201340 \u00b0C by linking a mutant coiled\u2010coil temperature\u2010responsive protein sensor to a synthetic transcription factor. To validate the construct, a HEAT\u2010transgenic monoclonal human cell line, FeverSense, is generated and it is confirmed that it works as a fever sensor that can temperature\u2010 and exposure\u2010time\u2010dependently trigger reporter gene expression in vitro and in vivo. For translational proof of concept, microencapsulated designer cells stably expressing a HEAT\u2010controlled insulin production cassette in a mouse model of type\u20101 diabetes are subcutaneously implanted and topical heating patches are used to apply heat corresponding to a warm sensation in humans. Insulin release is induced, restoring normoglycemia. Thus, HEAT appears to be suitable for practical electrothermal control of cell\u2010based therapy, and may also have potential for next\u2010generation treatment of fever\u2010associated medical conditions.<\/jats:p>","DOI":"10.1002\/advs.202101813","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T14:56:11Z","timestamp":1631112971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Genetically Encoded Protein Thermometer Enables Precise Electrothermal Control of Transgene Expression"],"prefix":"10.1002","volume":"8","author":[{"given":"Bozhidar\u2010Adrian","family":"Stefanov","sequence":"first","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysam","family":"Mansouri","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Bertschi","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Krawczyk","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine Charpin\u2010El","family":"Hamri","sequence":"additional","affiliation":[{"name":"D\u00e9partement G\u00e9nie Biologique Institut Universitaire de Technologie  Villeurbanne Cedex F\u201069622 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xue","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-667X","authenticated-orcid":false,"given":"Martin","family":"Fussenegger","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich Department of Biosystems Science and Engineering  Mattenstrasse 26 Basel 4058 Switzerland"},{"name":"University of Basel Faculty of Life Science  Basel 4056 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00780"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.037473"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114546"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.02.035"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-017-2102-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/aa9a6f"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19074"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2011.05.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025569"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20053-y"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2018.10.006"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aucc.2012.10.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1379\/CSC-278e.1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3658"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.02.025"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-019-1444-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80313-X"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00132"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.23.7033"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14468"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0956-5663(01)00226-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2690"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2233"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.9b00275"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/74493"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng069"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0501-8"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.0c00238"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/53\/13\/017"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/sb4000838"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3109\/02656736.2010.534527"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00541H"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/23328940.2016.1157668"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-014-0540-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.01.028"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.06.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11247"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0215-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203535"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9071(199610)50:2<152::AID-JMV8>3.0.CO;2-9"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.3.1265-1270.2000"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-010-0240-8"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903191"},{"key":"e_1_2_9_45_1","first-page":"e3801","author":"Duhan V.","year":"2012","journal-title":"J. Visualized Exp."},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.03.005"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt980"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3825"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0046-z"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7792603"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm466"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku545"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03486-y"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.12.006"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17183"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216753"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau7187"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-010-0218-8"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69547-1"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.02.022"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.7b00455"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.9b01005"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12583"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20171279"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2011.07.001"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1998.tb02195.x"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(98)00049-3"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00205.2002"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78355-6"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0602-592"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.01.011"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90219-3"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22020-6"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202101813","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202101813","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202101813","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:40:24Z","timestamp":1759776024000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202101813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,8]]},"references-count":74,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/advs.202101813"],"URL":"https:\/\/doi.org\/10.1002\/advs.202101813","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,8]]},"assertion":[{"value":"2021-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2101813"}}