A Responsive “Nano String Light” for Highly Efficient mRNA Imaging in Living Cells via Accelerated DNA Cascade Reaction

Nonenzymatic DNA catalytic amplification strategies have greatly benefited bioanalysis. However, long period incubation is usually required due to its relatively low reaction rate and efficiency, which limits its in vivo application. Here we design a responsive DNA nano string light (DNSL) by interval hybridization of modified hairpin DNA probe pairs to a DNA nanowire generated by rolling circle amplification and realize accelerated DNA cascade reaction (DCR) for fast and highly efficient mRNA imaging in living cells. Target mRNA initiates interval hybridization of two paired hairpin probes sequentially along the DNA nanowire and results in instant lighting up of the whole DNA nanowire with high signal gain due to the fast opening of all the self-quenched hairpins. The reaction time is about 6.7 times shorter compared with a regular DNA cascade reaction due to the acceleration based on domino effect. The cell delivery is achieved by modifying one of the hairpin probes with folic acid, and this intracellular imaging strategy is verified using human HeLa cells and intracellular survivin mRNA with a series of suppressed expressions as model, which provides a useful platform for fast and highly efficient detection of low-abundance nucleic acids in living cells.