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

Abstract 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.