A DNA‐Mediated Chemically Induced Dimerization (D‐CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior

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.