Biomedical Utility of Non‐Enzymatic DNA Amplification Reaction: From Material Design to Diagnosis and Treatment

Nucleic acid nanotechnology has become a promising strategy for disease diagnosis and treatment, owing to remarkable programmability, precision, and biocompatibility. However, current biosensing and biotherapy approaches by nucleic acids exhibit limitations in sensitivity, specificity, versatility, and real-time monitoring. DNA amplification reactions present an advantageous strategy to enhance the performance of biosensing and biotherapy platforms. Non-enzymatic DNA amplification reaction (NEDAR), such as hybridization chain reaction and catalytic hairpin assembly, operate via strand displacement. NEDAR presents distinct advantages over traditional enzymatic DNA amplification reactions, including simplified procedures, milder reaction conditions, higher specificity, enhanced controllability, and excellent versatility. Consequently, research focusing on NEDAR-based biosensing and biotherapy has garnered significant attention. NEDAR demonstrates high efficacy in detecting multiple types of biomarkers, including nucleic acids, small molecules, and proteins, with high sensitivity and specificity, enabling the parallel detection of multiple targets. Besides, NEDAR can strengthen drug therapy, cellular behavior control, and cell encapsulation. Moreover, NEDAR holds promise for constructing assembled diagnosis-treatment nanoplatforms in the forms of pure DNA nanostructures and hybrid nanomaterials, which offer utility in disease monitoring and precise treatment. Thus, this paper aims to comprehensively elucidate the reaction mechanism of NEDAR and review the substantial advancements in NEDAR-based diagnosis and treatment over the past five years, encompassing NEDAR-based design strategies, applications, and prospects.