A regenerated nanotweezer-managed catalytic DNA circuit for cancer-related sensing

Abstract

In this study, a regenerated nanotweezer-managed catalytic DNA circuit was constructed. A nanotweezer with two crossover motifs was assembled using 10 oligonucleotides, a toehold domain (TD), and a branch migration domain (BMD) as the two motifs of the nanotweezer. In the absence of a catalyst, the nanotweezer was opened, the TD and the BMD were separated with few catalytic activities. Upon catalyst addition, the set strand in the nanotweezer was liberated, forming a closed nanotweezer with proximal binding of the TD and the BMD with catalytic activity. Subsequently, the TD/BMD initiated the cyclic catalytic assembly of DNA hairpins, forming a DNA circuit. By re-introducing some set sequences, the nanotweezer and TD/BMD could be switched back to the opened state, and the progress of catalytic DNA circuit could be stopped and managed. By re-adding fresh catalysts, the stopped circuit could be re-initiated through regeneration of the closed nanotweezer. Thus, a controllable and flexible DNA circuit was achieved with sensitive and quantitative detection of cancer-related miRNA and uracil-DNA glycosylase (UDG) in complex biological samples. The novel system provid a flexible and reliable DNA circuit for biological detection, clinical diagnosis, and biomedical research.