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Non-invasive chemogenetics

Nature Biomedical Engineering volume 2, pages 467–468 (2018)Cite this article

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A technique combining focused ultrasound for opening the blood–brain barrier and virally encoded engineered G-protein-coupled receptors for promoting the expression of a gene targeting excitatory neurons enables the non-invasive stimulation of specific brain regions and cell types in mice.

Deciphering the roles of brain circuits in behaviour is a crucial first step for the development of therapeutic strategies to treat brain-related illnesses, such as mood disorders1 and neurodegenerative diseases2. Emerging therapies based on electrical stimulation, viral gene transfer or stem-cell replacement hold promise for the treatment of brain diseases, yet they often require invasive techniques such as stereotaxic surgery, which can damage tissue and initiate a long-lasting immune response. Also, conventional pharmacological approaches lack the spatial, temporal and cell-type specificity required to treat the brain, and can lead to deleterious side effects. Mikhail Shapiro and colleagues now report in Nature Biomedical Engineering a non-invasive approach that overcomes these limitations3. The technique, named acoustically targeted chemogenetics (ATAC), uses transient ultrasonic opening of the blood–brain barrier (BBB) to enable the targeted expression of an adeno-associated viral vector (AAV) encoding designer receptors exclusively activated by designer drugs (DREADDs) — a genetic system that utilizes orphan G-protein-coupled receptors that respond exclusively to the synthetic molecule clozapine-N-oxide (CNO) rather than to endogenous ligands4.

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Fig. 1: Experimental strategy for the ATAC-mediated interrogation of circuits in fear learning.

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Authors and Affiliations

  1. Department of Psychiatry and Neuroscience, Faculty of Medicine & CERVO Brain Research Center, Université Laval, Quebec City, Quebec, Canada

    Caroline Menard

  2. Department of Neuroscience, Center for Affective Neuroscience, and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA

    Scott J. Russo

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  1. Caroline Menard
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  2. Scott J. Russo
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Correspondence to Caroline Menard or Scott J. Russo.

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Menard, C., Russo, S.J. Non-invasive chemogenetics. Nat Biomed Eng 2, 467–468 (2018). https://doi.org/10.1038/s41551-018-0269-z

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