Journal
SCIENCE
Volume 341, Issue 6152, Pages 1358-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1235005
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Funding
- NIH
- NSF
- Defense Advanced Research Projects Agency
- Bill and Melinda Gates Foundation
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Engineering of cell fate through synthetic gene circuits requires methods to precisely implement control around native decision-making pathways and offers the potential to direct cell processes. We demonstrate a class of genetic control systems, molecular network diverters, that interface with a native signaling pathway to route cells to divergent fates in response to environmental signals without modification of native genetic material. A method for identifying control points within natural networks is described that enables the construction of synthetic control systems that activate or attenuate native pathways to direct cell fate. We integrate opposing genetic programs by developing network architectures for reduced antagonism and demonstrate rational tuning of performance. Extension of these control strategies to mammalian systems should facilitate the engineering of complex cellular signaling systems.
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