@article {64840,
	title = {Ultrapotent chemogenetics for research and potential clinical applications.},
	journal = {Science},
	volume = {364},
	year = {2019},
	month = {2019 Mar 14},
	pages = {eaav5282},
	abstract = {<p>Chemogenetics enables non-invasive chemical control over cell populations in behaving animals. However, existing small molecule agonists show insufficient potency or selectivity. There is also 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 anti-smoking drug varenicline. We then synthesized novel sub-nanomolar 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.</p>
},
	issn = {1095-9203},
	doi = {10.1126/science.aav5282},
	author = {Magnus, Christopher J and Lee, Peter H and Bonaventura, Jordi and Zemla, Roland and Gomez, Juan L and Ramirez, Melissa H and Hu, Xing and Galvan, Adriana and Basu, Jayeeta and Michaelides, Michael and Sternson, Scott M}
}
