The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
Unda S, Pomeranz L, Marongiu R, Yu X, Kelly L, Hassanzadeh G, Molina H, Vaisey G, Wang P, Dyke J, Fung E, Grosenick L, Zirkel R, Antoniazzi A, Norman S, Liston C, Schaffer C, Nishimura N, Stanley S, Friedman J, Kaplitt M
Journal
bioRxiv
Date Published
04/29/2024
Abstract
Here we report a novel suite of magnetogenetic tools, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. AAV-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine 2a receptor-cre driver mice resulted in motor freezing when placed in an MRI or adjacent to a transcranial magnetic stimulation (TMS) device. Functional imaging and fiber photometry both confirmed activation of the target region in response to the magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing cre into the globus pallidus led to similar circuit specificity and motor responses. Finally, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in subthalamic nucleus in PitX2-cre parkinsonian mice resulted in reduced local c-fos expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits non-invasively in-vivo using clinically available devices.