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Highly modular bow-tie gene circuits with programmable dynamic behaviour
DOI:10.1038/ncomms5729.png)
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
IF:
15.7
论文数:
9.4W
被引数:
91.2W
机构
引用论文
A single vector containing modified cre recombinase and LOX recombination sequences for inducible tissue-specific amplification of gene expression
NUCLEIC ACIDS RESEARCH
IF13.1
Temporal, spatial, and cell type-specific control of Cre-mediated DNA recombination in transgenic mice
NATURE BIOTECHNOLOGY
IF41.7

