Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 32, Pages 10226-10230Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201806155
Keywords
aptamers; cell behavior; chemically induced dimerization; DNAzymes; receptors
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Funding
- National Natural Science Foundation of China [21725503, 21575038]
- Foundation for Innovative Research Groups of NSFC [21521063]
- Young Top-notch Talent for Ten Thousand Talent Program
- Natural Science Foundation of Hunan Province [2015JJ1005]
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Small-molecule regulation is a powerful switching tool to manipulate cell signal transduction for a desired function; however, most available methods usually require genetic engineering to endow cells with responsiveness to user-defined small molecules. Herein, we demonstrate a nongenetic approach for small-molecule-controlled receptor activation and consequent cell behavior manipulation that is based on DNA-mediated chemically induced dimerization (D-CID). D-CID uses a programmable chemical-responsive DNA nanodevice to trigger DNA strand displacement and induce the activation of c-Met, a tyrosine kinase receptor cognate for hepatocyte growth factor, through dimerization. Through the use of various functional nucleic acids, including aptamers and DNAzymes, as recognition modules, the versatility of D-CID in inducing c-Met signaling upon addition of various small-molecular or ionic cues, including ATP, histidine, and Zn2+, is demonstrated. Moreover, owing its multi-input properties, D-CID can be used to manipulate the behaviors of multiple cell populations simultaneously in a selective and programmable fashion.
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