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Transferring a synthetic gene circuit from yeast to mammalian cells

Author

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  • Dmitry Nevozhay

    (The University of Texas MD Anderson Cancer Center
    School of Biomedicine, Far Eastern Federal University)

  • Tomasz Zal

    (The University of Texas MD Anderson Cancer Center)

  • Gábor Balázsi

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • Dmitry Nevozhay & Tomasz Zal & Gábor Balázsi, 2013. "Transferring a synthetic gene circuit from yeast to mammalian cells," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2471
    DOI: 10.1038/ncomms2471
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