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• W2564089345 abstract "By using tools from synthetic biology, sophisticated genetic devices can be assembled to reprogram mammalian cell activities. 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 the hybrid transcription factor TetR-ELK1, we assembled a synthetic insulin-sensitive transcription-control 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 hyperinsulinemia, 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." @default.
• W2564089345 created "2017-01-06" @default.
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• W2564089345 date "2016-12-19" @default.
• W2564089345 modified "2023-10-15" @default.
• W2564089345 title "Self-adjusting synthetic gene circuit for correcting insulin resistance" @default.
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• W2564089345 doi "https://doi.org/10.1038/s41551-016-0005" @default.
• W2564089345 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5412959" @default.
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• W2564089345 hasPublicationYear "2016" @default.
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