文献类型：期刊文献

英文题名：Synthetic dual-input mammalian genetic circuits enable tunable and stringent transcription control by chemical and light

作者：Chen, Xianjun[1,2,3];Li, Ting[1,2,3];Wang, Xue[1];Du, Zengmin[1,2,3];Liu, Renmei[1,2,3];Yang, Yi[1,2,3,4]

机构：[1]E China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg Technol, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, CAS Ctr Excellence Brain Sci, Optogenet & Mol Imaging Interdisciplinary Res Ctr, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Collaborat Innovat Ctr Genet & Dev, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2016

卷号：44

期号：6

起止页码：2677

外文期刊名：NUCLEIC ACIDS RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000374570500025)】；

基金：Funding for open access charge: 973 Program [2013CB531200]; NSFC [31225008, 91313301, 31170815, 31470833]; Shanghai Science and Technology Commission [12JC1402900, 11DZ2260600, 15YF1402600]; Dawn Program of the Shanghai Education Commission [11SG31]; State Key Laboratory of Bioreactor Engineering; 111 Project [B07023]; Fundamental Research Funds for the Central Universities.

语种：英文

摘要：Programmable transcription factors can enable precise control of gene expression triggered by a chemical inducer or light. To obtain versatile transgene system with combined benefits of a chemical inducer and light inducer, we created various chimeric promoters through the assembly of different copies of the tet operator and Gal4 operator module, which simultaneously responded to a tetracycline-responsive transcription factor and a light-switchable transactivator. The activities of these chimeric promoters can be regulated by tetracycline and blue light synergistically or antagonistically. Further studies of the antagonistic genetic circuit exhibited high spatiotemporal resolution and extremely low leaky expression, which therefore could be used to spatially and stringently control the expression of highly toxic protein Diphtheria toxin A for light regulated gene therapy. When transferring plasmids engineered for the gene switch-driven expression of a firefly luciferase (Fluc) into mice, the Fluc expression levels of the treated animals directly correlated with the tetracycline and light input program. We suggest that dual-input genetic circuits using TET and light that serve as triggers to achieve expression profiles may enable the design of robust therapeutic gene circuits for gene- and cell-based therapies.