title: Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles.
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.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stanley
authors.affiliation: Department of Chemical and Biological Engineering, Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sauer
authors.affiliation: Department of Chemical and Biological Engineering, Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kane
authors.affiliation: Department of Chemical and Biological Engineering, Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA.|Howard Hughes Medical Institute, New York, New York, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000528:radiation effects*; D005290:Ferric Compounds / Q000737:chemistry / Q000528:radiation effects; D005293:Ferritins / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000528:radiation effects*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D006706:Homeostasis / Q000528:radiation effects; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000528:radiation effects*; D051379:Mice; D011846:Radio Waves; D050916:TRPV Cation Channels / Q000737:chemistry / Q000235:genetics; D019076:Transgenes / Q000528:radiation effects
chemical_list: D001786:Blood Glucose; D005290:Ferric Compounds; D007328:Insulin; D058185:Magnetite Nanoparticles; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C494484:TRPV1 receptor; D049452:Green Fluorescent Proteins; C000499:ferric oxide; D005293:Ferritins; D005947:Glucose