小RNA
计算生物学
生物标志物
纳米器件
生物
细胞生物学
基因
纳米技术
遗传学
材料科学
作者
Fang He,Meixia Wang,Jieyu Wang,Hong‐Hui Wang,Zhou Nie
标识
DOI:10.1002/anie.202305227
摘要
Abstract MicroRNAs (miRNAs) have emerged as promising diagnostic biomarkers and therapeutic targets in various diseases. However, there is currently a lack of molecular strategies that can effectively use disease‐associated extracellular miRNAs as input signals to drive therapeutic functions. Herein, we present a modular and programmable miRNA‐responsive chimeric DNA receptor (miRNA‐CDR) capable of biomarker‐driven therapy. By grafting a miRNA‐responsive DNA nanodevice on a natural membrane receptor via aptamer anchoring, miRNA‐CDR can sense extracellular miRNA levels and autonomously induce dimerization‐mediated receptor activation via the complementary‐mediated strand displacement reaction‐induced dynamic DNA assembly. The sequence programmability of miRNA‐CDR allows it to sense and respond to a user‐defined miRNA with tunable sensitivity. Moreover, the miRNA‐CDR is versatile and customizable to reprogram desirable signaling output via adapting a designated receptor, such as MET and FGFR1. Using a mouse model of drug‐induced acute liver injury (DILI), we demonstrate the functionality of a designer miRNA‐CDR in rewiring the recognition of the DILI‐elevated miR‐122 to promote MET signaling of hepatocytes for biomarker‐driven in situ repair and liver function restoration. Our synthetic miRNA‐CDR platform provides a novel molecular device enabling biomarker‐driven therapeutic cellular response, potentially paving the way for improving the precision of cell therapy in regenerative medicine.
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