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Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles

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A Corrigendum to this article was published on 07 May 2015

This article has been updated

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.

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Figure 1: In vitro optimization of gene expression and protein release with genetically encoded nanoparticles.
Figure 2: RF-regulated gene expression in vivo using MSCs.
Figure 3: RF-regulated gene expression in vivo using adenoviral delivery of transgenes.
Figure 4: Repeated RF treatment to regulate protein delivery.
Figure 5: Remote activation of gene expression with a static magnetic field.

Change history

  • 20 February 2015

     In the version of this article initially published, the ferritin linker region was incorrectly described as HA-tagged. It was FLAG-tagged. Thus, the descriptions of its detection in the study and of the protocol used for its detection in the Online Methods were incorrect (including an incorrect reference for the associated antibody used). Also, the description of the development of the tag was missing from the Online Methods. The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We would like to thank Friedman laboratory members for helpful discussions and S. Korres for assistance with preparation and submission of the manuscript. This work was funded by the Howard Hughes Medical Institute, the JPB Foundation, the US National Institutes of Health (GM095654) and a Rensselaer Fellowship (to J.S.) under a US National Institutes of Health predoctoral training grant (GM067545).

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J.M.F. conceived the project, and J.M.F. and J.S.D. supervised the studies. S.A.S. and J.S. designed and performed the experiments. R.S.K. provided technical advice. S.A.S., J.S., J.S.D. and J.M.F. wrote the manuscript.

Corresponding authors

Correspondence to Jonathan S Dordick or Jeffrey M Friedman.

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The authors declare no competing financial interests.

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Stanley, S., Sauer, J., Kane, R. et al. Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles. Nat Med 21, 92–98 (2015). https://doi.org/10.1038/nm.3730

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