A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells

Müller, Konrad and Engesser, Raphael and Metzger, Stéphanie and Kämpf, Michael M. and Busacker, Moritz and Nagy, Ferenc István (2013) A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells. NUCLEIC ACIDS RESEARCH, 41 (7). 3-11, (e77). ISSN 0305-1048

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Abstract

Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.

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