On‐Site Non‐enzymatic Orthogonal Activation of a Catalytic DNA Circuit for Self‐Reinforced In Vivo MicroRNA Imaging

The wide extracellular-intracellular distribution of microRNA requires the on-site, robust and efficient activation of catalytic DNA circuits inside live cells. Herein, we develop an efficient non-enzymatic circuitry activation strategy to realize the orthogonally controlled catalytic DNA (CCD) circuit for achieving high-fidelity in vivo microRNA imaging through multiply guaranteed molecular recognition and progressively accelerated signal amplification. For predictable on-site activation and useful catalytic efficiency, the dominating circuitry fuel strand was initially split into inactive fuel subunits that were grafted into an auxiliary catalytic circuit. There, the in-cell-specific mRNA triggered the orthogonal amplification of the active fuel strands for sensitive target detection through the chief entropy-driven catalytic DNA circuit. We believe that the on-site orthogonal circuitry activation method can contribute to clinical diagnosis and prognosis.