Nucleic acid-templated chemical reactions for nucleic acid detection

Abstract

Nucleic acid-templated reactions are chemical processes driven by the increased effective concentration of reactants on nucleic acids through the sequence-specific hybridization of nucleic acids. Because these reactions translate the signals of target nucleic acids to detectable specific outputs, such as fluorescence, they can be applied for nucleic acid sensing and imaging. Owing to their advantageous features, such as signal amplification, isothermal nonenzymatic operation, and diverse reaction outputs and designs, the templated reactions have considerable potential for designing next-generation nucleic acid sensors with high sensitivity, selectivity, rapidity, and user-friendliness. Thus, over the past two decades, numerous templated reactions have been developed for more efficient nucleic acid detection. This review highlights recent advances in nucleic acid-templated reactions since 2020, focusing on the newly developed reactions and strategies for designing highly sensitive, selective, and accurate nucleic acid sensing systems. We also summarize templated reaction research since 2015 and explore how integrating these reactions with other signal amplification systems and readout methods has led to the development of practical nucleic acid sensors with improved properties. According to the analysis of each type of templated reactions (ligation, releasing, and transformation), design trends are discussed that inform the outlook for the future development of nucleic acid sensors utilizing templated reactions.