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Science 332 (6037): 1565-1568

Copyright © 2011 by the American Association for the Advancement of Science

A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice

Haifeng Ye,1 Marie Daoud-El Baba,2 Ren-Wang Peng,1 Martin Fussenegger1,3,*

Abstract: Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse–transcription converters may have applications in therapeutics and protein expression technology.

1 Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
2 Département Génie Biologique, Institut Universitaire de Technologie (IUT), F-69622 Villeurbanne Cedex, France.
3 Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.

* To whom correspondence should be addressed. E-mail: fussenegger{at}bsse.ethz.ch

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