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Updated: Jan 27, 2026

Human Egg Maturity Assessment and Its Clinical Application
Published on: August 19, 2019
Ultrapotent chemogenetics for research and potential clinical applications
Christopher J Magnus1, Peter H Lee1, Jordi Bonaventura2
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Abstract:
Chemogenetics enables noninvasive chemical control over cell populations in behaving animals. However, existing small-molecule agonists show insufficient potency or selectivity. There is also a need for chemogenetic systems compatible with both research and human therapeutic applications. We developed a new ion channel-based platform for cell activation and silencing that is controlled by low doses of the smoking cessation drug varenicline. We then synthesized subnanomolar-potency agonists, called uPSEMs, with high selectivity for the chemogenetic receptors. uPSEMs and their receptors were characterized in brains of mice and a rhesus monkey by in vivo electrophysiology, calcium imaging, positron emission tomography, behavioral efficacy testing, and receptor counterscreening. This platform of receptors and selective ultrapotent agonists enables potential research and clinical applications of chemogenetics.
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