Catalytic DNA for Precision Diagnostics: DNAzyme-Based Approaches to Single-Nucleotide Polymorphism Detection

Single-nucleotide polymorphisms (SNPs) are the most abundant form of human genetic variation and serve as important biomarkers in disease risk assessment, therapeutic stratification, and precision medicine. Yet accurate detection of low-abundance SNPs in complex biological samples remains difficult with many conventional genotyping methods, which often rely on sophisticated instrumentation and show limited tolerance to matrix interference. DNAzyme-based biosensors offer a promising alternative by coupling programmable nucleic acid recognition with catalytic signal generation under isothermal conditions. This review highlights recent advances in DNAzyme-based SNP detection across optical, electrochemical, and amplification-assisted formats, including fluorescence, colorimetric, chemiluminescent, rolling circle amplification, loop-mediated isothermal amplification, hybridization chain reaction, and catalytic hairpin assembly strategies. We also discuss molecular design principles that enhance single-base discrimination, such as binding-arm engineering, cofactor tuning, and computational sequence design. Finally, we outline current limitations, including nuclease susceptibility, temperature dependence, and performance in complex sample matrices, and consider emerging opportunities for DNAzyme-enabled SNP analysis in point-of-care diagnostics, personalized medicine, and large-scale genomics.