Transferring a synthetic gene circuit from yeast to mammalian cells

Dmitry Nevozhay, Tomasz Zal and Gábor Balázsi ()
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Dmitry Nevozhay: The University of Texas MD Anderson Cancer Center
Tomasz Zal: The University of Texas MD Anderson Cancer Center
Gábor Balázsi: The University of Texas MD Anderson Cancer Center

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: Abstract The emerging field of synthetic biology builds gene circuits for scientific, industrial and therapeutic needs. Adaptability of synthetic gene circuits across different organisms could enable a synthetic biology pipeline, where circuits are designed in silico, characterized in microbes and reimplemented in mammalian settings for practical usage. However, the processes affecting gene circuit adaptability have not been systematically investigated. Here we construct a mammalian version of a negative feedback-based ‘linearizer’ gene circuit previously developed in yeast. The first naïve mammalian prototype was non-functional, but a computational model suggested that we could recover function by improving gene expression and protein localization. After rationally developing and combining new parts as the model suggested, we regained function and could tune target gene expression in human cells linearly and precisely as in yeast. The steps we have taken should be generally relevant for transferring any gene circuit from yeast into mammalian cells.

Date: 2013
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DOI: 10.1038/ncomms2471

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