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10.1038/ncomms5729

http://scihub22266oqcxt.onion/10.1038/ncomms5729
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C4197411!4197411!25311543
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suck abstract from ncbi


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pmid25311543      Nat+Commun 2014 ; 5 (ä): 4729
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  • Highly modular bow-tie gene circuits with programmable dynamic behavior #MMPMID25311543
  • Prochazka L; Angelici B; Häfliger B; Benenson Y
  • Nat Commun 2014[]; 5 (ä): 4729 PMID25311543show ga
  • Synthetic gene circuits often require extensive mutual optimization of their components for successful operation, while modular and programmable design platforms are rare. A possible solution lies in the ?bow-tie? architecture, which stipulates a focal component - a ?knot? - uncoupling circuits? inputs and outputs, simplifying component swapping, and introducing additional layer of control. Here we construct, in cultured human cells, synthetic bow-tie circuits that transduce microRNA inputs into protein outputs with independently programmable logical and dynamic behavior. The latter is adjusted via two different knot configurations: a transcriptional activator causing the outputs to track input changes reversibly, and a recombinase-based cascade, converting transient inputs into permanent actuation. We characterize the circuits in HEK293 cells, confirming their modularity and scalability, and validate them using endogenous microRNA inputs in additional cell lines. This platform can be used for biotechnological and biomedical applications in vitro, in vivo, and potentially in human therapy.
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