Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / radiation effects*
  • Ferric Compounds / chemistry
  • Ferric Compounds / radiation effects
  • Ferritins / chemistry
  • Ferritins / genetics
  • Gene Expression Regulation / radiation effects*
  • Glucose / genetics
  • Glucose / metabolism*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / radiation effects
  • Homeostasis / radiation effects
  • Insulin / biosynthesis*
  • Insulin / genetics
  • Insulin / radiation effects
  • Magnetite Nanoparticles / chemistry
  • Magnetite Nanoparticles / radiation effects*
  • Mice
  • Radio Waves
  • TRPV Cation Channels / chemistry
  • TRPV Cation Channels / genetics
  • Transgenes / radiation effects


  • Blood Glucose
  • Ferric Compounds
  • Insulin
  • Magnetite Nanoparticles
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • TRPV1 receptor
  • Green Fluorescent Proteins
  • ferric oxide
  • Ferritins
  • Glucose