期刊
NATURE BIOMEDICAL ENGINEERING
卷 1, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41551-016-0005
关键词
-
资金
- European Research Council (ERC) advanced grant [321381]
- Cantons of Basel
- Cantons of Swiss Confederation within the INTERREG IV A.20 tri-national research program
- National Key Research and Development Program of China, Stem Cell and Translational Research [2016YFA0100300]
- National Natural Science Foundation of China (NSFC) [31470834, 31522017, 31670869]
- Science and Technology Commission of Shanghai Municipality [15QA1401500, 14JC1401700]
- Thousand Youth Talents Plan
Sophisticated genetic devices can be assembled to reprogram mammalian cell activities using tools from synthetic biology. Here, we demonstrate that a self-adjusting synthetic gene circuit can be designed to sense and reverse the insulin-resistance syndrome in different mouse models. By functionally rewiring the mitogen-activated protein kinase (MAPK) signalling pathway to produce MAPK-mediated activation of a hybrid transcription factor consisting of the tetracycline repressor, TetR, fused to the human ELK1-derived transactivation domain (TetR-Elk1), we assembled a synthetic insulin-sensitive transcriptioncontrol device that self-sufficiently distinguished between physiological and increased blood insulin levels and correspondingly fine-tuned the reversible expression of therapeutic transgenes from synthetic TetR-ELK1-specific promoters. In acute experimental hyperinsulinaemia, the synthetic insulin-sensing designer circuit reversed the insulin-resistance syndrome by coordinating expression of the insulin-sensitizing compound adiponectin. Engineering synthetic gene circuits to sense pathologic markers and coordinate the expression of therapeutic transgenes may provide opportunities for future gene-and cell-based treatments of multifactorial metabolic disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据