Scaling up of a Self‐Confined Catalytic Hybridization Circuit for Robust microRNA Imaging

Abstract

The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through a concatenated chemical reaction network has rarely been reported to mimic dynamic self‐assembly system. Herein, a catalytic self‐defined circuit (CSC) for the hierarchically concatenated assembly of DNA domino nanostructures is engineered. By incorporating pre‐sealed symmetrical fragments into the preying hairpin reactants, the CSC system allows the hierarchical DNA self‐assembly via a microRNA (miRNA)‐powered self‐sorting catalytic hybridization reaction. With minimal strand complexity, this self‐sustainable CSC system streamlined the circuit component and achieved localization‐intensified cascaded signal amplification. Profiting from the self‐adaptively concatenated hybridization reaction, a reliable and robust method has been achieved for discriminating carcinoma tissues from the corresponding para‐carcinoma tissues. The CSC‐sustained self‐assembly strategy provides a comprehensive and smart toolbox for organizing various hierarchical DNA nanostructures, which may facilitate more insights for clinical diagnosis and therapeutic assessment.

A Methylation-Gated DNAzyme Circuit for Spatially Controlled Imaging of MicroRNA in Cells and Animals

“…As a typical artificial molecular self-assembly network, − DNA circuits have been utilized for intelligent biosensing and biocomputing applications − based on their intrinsic multiply guaranteed and amplified molecular recognitions. − To eliminate the undesirable disturbance from a surrounding complex biological environment, the endogenously stimulated DNA circuits are thus developed for achieving the site-specific circuitry activation with high spatiotemporal controllability, − and these include small molecules (e.g., ATP), , RNAs, − and enzymes. − The small molecule-based regulation strategies were constrained by the insufficient aptamers with low binding affinities . Meanwhile, the RNA regulation methods are confronted with inefficient regulation capacities as a result of their low expressions in live cells .…”

Endogenous Glutathione-Activated Nucleic Acid Molecular Circuitry for Cell-Specific MicroRNA Imaging

“…However, these methods can only be applied in vitro and cannot perform living cell analysis of miRNAs. Currently, analysis of miRNAs in living cells − or even in vivo − has developed into a research focus, as it offers comprehensive information about the quantity, location, and regulation of biomolecules. Traditional cell imaging techniques, e.g ., fluorescence in situ hybridization (FISH), are limited by their inadequate amplification efficiency .…”