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A Red/far-red Light-responsive Bi-stable Toggle Switch to Control Gene Expression in Mammalian Cells
Konrad Müller
Raphael Engesser
Stephanie Metzger
Simon Schulz
Michael M. Kämpf
Moritz Busacker
Thorsten Steinberg
Pascal Tomakidi
Martin Ehrbar
Ferenc Nagy
Jens Timmer
Matias D. Zubriggen
Wilfried Weber
出版
Universität
, 2013
URL
http://books.google.com.hk/books?id=TjY30AEACAAJ&hl=&source=gbs_api
註釋
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