State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, 410082, P. R. China.
Angew Chem Int Ed Engl. 2018 Aug 6;57(32):10226-10230. doi: 10.1002/anie.201806155. Epub 2018 Jul 15.
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 Zn , 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.
小分子调控是一种强大的开关工具，可用于操纵细胞信号转导以实现预期功能；然而，大多数现有方法通常需要基因工程来赋予细胞对用户定义的小分子的响应能力。在此，我们展示了一种基于 DNA 介导的化学诱导二聚化（D-CID）的非遗传方法，用于控制小分子激活受体以及随后的细胞行为操作。D-CID 使用可编程的化学响应 DNA 纳米器件来触发 DNA 链置换，并通过二聚化诱导肝细胞生长因子的酪氨酸激酶受体 c-Met 的激活。通过使用各种功能核酸，包括适体和 DNA 酶作为识别模块，证明了 D-CID 在添加各种小分子或离子线索（包括 ATP、组氨酸和 Zn ）时诱导 c-Met 信号的多功能性。此外，由于其多输入特性，D-CID 可用于以选择性和可编程的方式同时操纵多个细胞群体的行为。
