Research Article

Ultrapotent chemogenetics for research and potential clinical applications

See allHide authors and affiliations

Science  12 Apr 2019:
Vol. 364, Issue 6436, eaav5282
DOI: 10.1126/science.aav5282

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Improved agonists for chemogenetics

Targeting ligand-responsive receptors to specific groups of cells, a strategy known as chemogenetics, is a powerful tool in many neurological applications. There is increasing interest in extending these tools for human treatment. Magnus et al. designed chemogenetic ion channels that improve currently available systems and are activated by the clinically used antismoking drug varenicline. They engineered a ligand-binding domain less responsive to endogenous signals and identified agonists that function at nanomolar concentrations. The combination of drug and introduced channels transiently silenced neurons, with slow but effective washout, and induced behavioral changes in animal models after brain administration.

Science, this issue p. eaav5282