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Functional DNAzyme-Guided Target Identification and Portable Detection of Colorectal Cancer
Yu Yan1, Hao Zheng1, Shenyang Zhao2
1State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, the International Peace Maternity and Child Health Hospital, School of Medicine, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
None:
Rapid discrimination of colorectal cancer (CRC) at the time of tissue sampling remains clinically challenging. Although DNAzyme-based assays enable selective analysis of complex biological samples, their diagnostic translation is constrained by undefined endogenous activators. Here, using an iterative DNAzyme activity-guided isolation strategy that integrates chromatographic fractionation with affinity enrichment, we identified malic enzyme 1 (ME1) as the molecular activator of a DNAzyme newly selected against colorectal cancer tissue lysates. The ME1-triggered catalytic reaction was then translated into a lateral flow format, enabling instrument-free visual detection within 35 min. In clinical specimens, the platform discriminated CRC from low- and high-grade intraepithelial neoplasia with an AUC of 0.98. By defining the molecular basis of DNAzyme activation and coupling it to a portable readout, this work provides a direct route from evolving DNAzyme probes for sensing complex tissues to rapid, near-point-of-care detection of CRC.
