文献类型：期刊文献

英文题名：A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice

作者：Li, Ting[1,2];Chen, Xianjun[1,2,3];Qian, Yajie[1,2];Shao, Jiawei[4,5];Li, Xie[1,2];Liu, Shuning[1,2];Zhu, Linyong[1];Zhao, Yuzheng[1,2];Ye, Haifeng[4,5];Yang, Yi[1,2,3,5]

机构：[1]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ct, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg Technol, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai 200031, Peoples R China;[4]East China Normal Univ, Synthet Biol & Biomed Engn Lab, Biomed Synthet Biol Res Ctr, Shanghai Key Lab Regulatory Biol,Inst Biomed Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China;[5]East China Normal Univ, Sch Life Sci, Dongchuan Rd 500, Shanghai 200241, Peoples R China

年份：2021

卷号：12

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000614500600015)】；

基金：We thank Dr. Huan Xu at East China University of Science and Technology, Jianli Yin, Shuai Xue, Guiling Yu, Yang Zhou at East China Normal University for technical assistance. This research was supported by the National Key Research and Development Program of China (2019YFA0904800 and 2017YFA050400 to Y.Y., 2019YFA0904500 to H.Y.), NSFC (91857202 and 21937004 to Y.Y., 31971349 and 31600688 to X.C. and 31901033 to T.L.), the Shanghai Science and Technology Commission (18JC1411900 to Y.Y., 19ZR1472800 to X.C. and 18JC1411000 to H.Y.), the Shanghai Rising-Star Program to X.C., the Young Elite Scientists Sponsorship Program by CAST to X.C, the Shanghai Sailing Program (19YF1411300 to T.L.), the Fundamental Research Funds for the Central Universities to Y.Y. and X.C., the China Postdoctoral Science Foundation (2019M651413 to T.L.).

语种：英文

摘要：Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future. Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in diverse cellular activities. Here the authors show a synthetic BRET-based transgene expression system that allows pulsatile and quantitative activation of gene expression both in live cells and in vivo.