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Nat Med. 2015 Jan;21(1):92-98. doi: 10.1038/nm.3730. Epub 2014 Dec 15.

Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles.

Author information

1
Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA.
2
Department of Chemical and Biological Engineering, Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
3
Howard Hughes Medical Institute, New York, New York, USA.
#
Contributed equally

Abstract

Means for temporally regulating gene expression and cellular activity are invaluable for elucidating underlying physiological processes and would have therapeutic implications. Here we report the development of a genetically encoded system for remote regulation of gene expression by low-frequency radio waves (RFs) or a magnetic field. Iron oxide nanoparticles are synthesized intracellularly as a GFP-tagged ferritin heavy and light chain fusion. The ferritin nanoparticles associate with a camelid anti-GFP-transient receptor potential vanilloid 1 fusion protein, αGFP-TRPV1, and can transduce noninvasive RF or magnetic fields into channel activation, also showing that TRPV1 can transduce a mechanical stimulus. This, in turn, initiates calcium-dependent transgene expression. In mice with stem cell or viral expression of these genetically encoded components, remote stimulation of insulin transgene expression with RF or a magnet lowers blood glucose. This robust, repeatable method for remote regulation in vivo may ultimately have applications in basic science, technology and therapeutics.

PMID:
25501906
PMCID:
PMC4894538
DOI:
10.1038/nm.3730
[Indexed for MEDLINE]
Free PMC Article

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