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.

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes

“…The choice of sample size was based on published reports of quantifying diabetic symptoms in mice. 72 Comparisons among groups were performed using Student's t test, and the results were expressed as the means ± SEM. All mice were sacrificed after termination of experiments.…”

Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields

“…The paramagnetic protein ferritin was recently used as substitute for MNPs. Stanley et al developed a genetically encoded system where GFP-tagged ferritin associated intracellularly with a camelid anti-GFP-TRPV1 fusion protein, which can activate ion channel by the interaction of ferritin with noninvasive radio waves (25.6 kA/m, 465 kHz) [78]. They also demonstrated that the system could be used to lower blood glucose by remotely stimulating insulin transgene expression with a radio-frequency magnetic field [78].…”

“…Stanley et al developed a genetically encoded system where GFP-tagged ferritin associated intracellularly with a camelid anti-GFP-TRPV1 fusion protein, which can activate ion channel by the interaction of ferritin with noninvasive radio waves (25.6 kA/m, 465 kHz) [78]. They also demonstrated that the system could be used to lower blood glucose by remotely stimulating insulin transgene expression with a radio-frequency magnetic field [78]. Later the same group improved the genetically encoded system for noninvasive, temporal activation or inhibition of neuronal activity in vivo by radio-frequency treatment and described its use to study central nervous system control of glucose homeostasis and feeding in mice [79].…”

Radio Signals from the DNA: A Philosophical Issue

“…In 2014, a research paper was published in Nature Genetics which launched a new direction in optogenetics which is known as radiogenetics (Stanley et al 2014). Radiogenetics will make it possible to remotely control biological targets in living animals without wires, implants, or drugs.…”