脱甲基酶
化学
小RNA
生物正交化学
表观遗传学
生物分子
细胞生物学
计算生物学
纳米技术
生物化学
生物
组合化学
基因
点击化学
材料科学
作者
Yuxuan Zhu,Ruomeng Li,Yifei Wang,Qingqing Zhang,Yuqiu He,Jinhua Shang,Xiaoqing Liu,Fuan Wang
标识
DOI:10.1021/acs.analchem.4c01556
摘要
Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.
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