Recent development of nucleic acid nanosensors to detect sequence-specific binding interactions: From metal ions, small molecules to proteins and pathogens

DNA carries important genetic instructions and plays vital roles in regulating biological activities in living cells. Proteins such as transcription factors binds to DNA to regulate the biological functions of DNA, and similarly many drug molecules also bind to DNA to modulate its functions. Due to the importance of protein-DNA and drug-DNA binding, there has been intense effort in developing novel nanosensors in the same length scale as DNA, to effectively study these binding interactions in details. In addition, aptamers can be artificially selected to detect metal ions and pathogens such as bacteria and viruses, making nucleic acid nanosensors more versatile in detecting a large variety of analytes. In this minireview, we first explained the different types and binding modes of protein-DNA and drug-DNA interactions in the biological systems, as well as aptamer-target binding. This was followed by the review of five types of nucleic acid nanosensors based on optical or electrochemical detection. The five types of nucleic acid nanosensors utilizing colorimetric, dynamic light scattering (DLS), surface-enhanced Raman spectroscopy (SERS), fluorescence and electrochemical detections have been recently developed to tackle some of the challenges in high-throughput screening technology for large scale analysis, which is especially useful for drug development and mass screening for pandemic outbreak such as SARS or COVID-19.