{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T22:01:28Z","timestamp":1767996088787,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390895286"],"award-info":[{"award-number":["390895286"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The use of optogenetic tools offers an excellent method for spatially and temporally regulated gene and protein expression in cell therapeutic approaches. This could be useful as a concomitant therapeutic measure, especially in small body compartments such as the inner ear, for example, during cochlea implantation, to enhance neuronal cell survival and function. Here, we used the blue light activatable CRY2\/CIB system to induce transcription of brain\u2010derived neurotrophic factor (BDNF) in human cells. Transfection with three plasmids, encoding for the optogenetic system and the target, as well as illumination protocols were optimized with luciferase as a reporter to achieve the highest protein expression in human embryonic kidney cells 293. Illumination was performed either with a light\u2010emitting diode or with a scanning laser setup. The optimized protocols were applied for the production of BDNF. We could demonstrate a 64.7\u2010fold increase of BNDF expression upon light induction compared to the basal level. Light\u2010induced BDNF was biologically active and enhanced survival and neurite growth of spiral ganglion neurons. The optogenetic approach can be transferred to autologous cell systems, such as bone marrow\u2010derived mesenchymal stem cells, and thus represents the first optogenetic neurotrophic therapy for the inner ear.<\/jats:p>","DOI":"10.1002\/biot.202400384","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T23:31:52Z","timestamp":1735255912000},"source":"Crossref","is-referenced-by-count":2,"title":["Blue Light\u2010Induced, Dosed Protein Expression of Active BDNF in Human Cells Using the Optogenetic CRY2\/CIB System"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5942-0340","authenticated-orcid":false,"given":"Sina","family":"Christoffers","sequence":"first","affiliation":[{"name":"Institute of Technical Chemistry Leibniz University Hannover  Hannover Germany"},{"name":"Cluster of Excellence Hearing4all  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Wichert","sequence":"additional","affiliation":[{"name":"Institute of Technical Chemistry Leibniz University Hannover  Hannover Germany"},{"name":"Cluster of Excellence Hearing4all  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Wiebe","sequence":"additional","affiliation":[{"name":"Institute of Technical Chemistry Leibniz University Hannover  Hannover Germany"},{"name":"Cluster of Excellence Hearing4all  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Leilani","family":"Torres\u2010Mapa","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Institute of Quantum Optics Leibniz University Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Goblet","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Harre","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Department of Otorhinolaryngology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3397-3082","authenticated-orcid":false,"given":"Odett","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Department of Otorhinolaryngology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc\u2010Nils","family":"Wahalla","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Institute of Microelectronic Systems Leibniz University Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Blume","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Institute of Microelectronic Systems Leibniz University Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Heisterkamp","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Institute of Quantum Optics Leibniz University Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasia","family":"Warnecke","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Hearing4all  Hannover Germany"},{"name":"Department of Otorhinolaryngology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-4884","authenticated-orcid":false,"given":"Cornelia","family":"Blume","sequence":"additional","affiliation":[{"name":"Institute of Technical Chemistry Leibniz University Hannover  Hannover Germany"},{"name":"Cluster of Excellence Hearing4all  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3111"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27895"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1524"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx804"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1569"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201000648\u20108"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3065667"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.104.025643"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt002"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12955"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1143274"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010021\u201001036\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010023\u201001764\u20108"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.038"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00477"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/374450a0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2015.56342"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.677"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2016.1183641"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14630"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009980\u20107"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012387"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1088\/0022\u20103727\/47\/20\/205401"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1088\/1361\u20106439\/ab2a53"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00659"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28141"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24488"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0386\u201019.2019"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23360"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010022\u201003744\u20102"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2019.04.015"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306\u20104522(99)00296\u20101"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126827"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2008.08.005"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051145"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165764"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201004146\u20103"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2015.03.005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.05.028"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41377-020-0268-1"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao0540"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx260"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401343101"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.262"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10542"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1364\/OE.464409"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010011\u20101155\u20100"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102002\u20103\u20107\u2010research0034"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.202400384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:22:16Z","timestamp":1759954936000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.202400384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/biot.202400384"],"URL":"https:\/\/doi.org\/10.1002\/biot.202400384","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"article-number":"e202400384"}}