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Highly modular bow-tie gene circuits with programmable dynamic behaviour

delete2014-10-14
delete33
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OA
AI
L
Laura Prochazka
B
Bartolomeo Angelici
B
Benjamin Haefliger
Y
Yaakov Benenson *
DOI:10.1038/ncomms5729delete
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摘要

摘要

En 中文
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 behaviour. 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.
Keyword:
SITE-SPECIFIC RECOMBINATION
MAMMALIAN-CELLS
CONDITIONAL EXPRESSION
TRANSGENE EXPRESSION
ACTIVATION DOMAIN
CRE RECOMBINASE
STEM-CELLS
MICRORNA
TISSUE
MICE
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期刊

Nature Communications 封面图
Nature Communications
IF:
15.7
论文数:
9.4W
被引数:
91.2W

机构

S
swiss federal institutes of technology domain
学者数:
795
论文数: 1.1K
被引数: 0
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