Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders

Jingwei Song; Ruchit V Patel; Massoud Sharif; Anagha Ashokan; Michael Michaelides

doi:10.1016/j.ymthe.2021.11.019

Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders

Mol Ther. 2022 Mar 2;30(3):990-1005. doi: 10.1016/j.ymthe.2021.11.019. Epub 2021 Dec 1.

Authors

Jingwei Song¹, Ruchit V Patel², Massoud Sharif³, Anagha Ashokan³, Michael Michaelides⁴

Affiliations

¹ National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: jsong64@jh.edu.
² Harvard Medical School, Boston, MA 02115, USA.
³ Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218, USA.
⁴ National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA; Department of Psychiatry & Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Electronic address: mike.michaelides@nih.gov.

Abstract

Chemogenetics enables precise, non-invasive, and reversible modulation of neural activity via the activation of engineered receptors that are pharmacologically selective to endogenous or exogenous ligands. With recent advances in therapeutic gene delivery, chemogenetics is poised to support novel interventions against neuropsychiatric diseases and disorders. To evaluate its translational potential, we performed a scoping review of applications of chemogenetics that led to the reversal of molecular and behavioral deficits in studies relevant to neuropsychiatric diseases and disorders. In this review, we present these findings and discuss the potential and challenges for using chemogenetics as a precision medicine-based neuromodulation strategy.

Keywords: DREADDs; chemogenetics; gene delivery; gene therapy; neuromodulation; neurotherapeutics.

Publication types

Research Support, N.I.H., Intramural
Review

MeSH terms

Genetic Therapy*
Ligands

Substances

Ligands

Grants and funding

ZIA DA000069/ImNIH/Intramural NIH HHS/United States