Three-dimensional DNA tweezers serve as modular DNA intelligent machines for detection and regulation of intracellular microRNA

MicroRNAs (miRNAs) as novel biological targets are hardly applied in diagnostic and treatment of diseases, as they are difficult to be accurately detected and regulated. Here, we demonstrated a modular DNA intelligent machine named three-dimensional tweezers (TD-tweezers) to image and regulate miRNAs in living cells simultaneously. Fluorophore or miRNA inhibitors are introduced as detecting or regulating parts to construct different types of TD-tweezers, and the conformational state of TD-tweezers is controlled by the target miRNAs. The TD-tweezers exhibit excellent sensitivity, specificity, stability, and biocompatibility in vitro and in vivo, and their function of regulating miRNAs was confirmed by the up-regulated expression of downstream genes and proteins. Moreover, the TD-tweezers have been tested in whole blood, preliminarily verifying their clinical application potential. This design provides a multifunctional platform that can achieve efficient detection and regulation of targets within living cells and promote the development of DNA intelligent machines.