The ability to temporally regulate gene expression and cellular activity is invaluable for determining underlying physiological processes and has therapeutic implications. We have developed a system for remote regulation of gene expression by low frequency radiowaves (RF) or a static magnetic field. Herein we describe a remote activation scheme by which Transient Receptor Potential Vanilloid 1 (TRPV1) calcium channel is gated by a tethered magnetic nanoparticle in an external magnetic field. The magnetic particle can either tether to an extracellular loop of the channel via a His6 antibody, or can be synthesized internally as a GFP-tagged ferritin heavy and light chain fusion. The ferritin nanoparticles associate with a camelid anti-GFP-TRPV1 fusion protein. Upon exposure to a static or time-varying magnetic field, the nanoparticle transduces energy to the channel, causing opening and subsequent calcium flux, which in turn promotes 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. Additionally, this work investigates the contributions of heat and mechanical strain by an RF irradiated iron-oxide particle to determine dominant mechanism of channel opening. This robust, repeatable method for remote regulation in vivo may ultimately have applications in basic science, technology and therapeutics.

Remote activation of TRPV1 for therapeutic effect

249th National Meeting (2015)

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