Nucleic acid-assisted CRISPR-Cas systems for advanced biosensing and bioimaging

Nucleic acid molecules possess many superior properties, including high designability and structural predictability, making them attractive biosensing and bioimaging tools. The CRISPR-Cas systems can recognize and cleave nucleic acid targets with high programmability and flexibility, and have been engineered as a multifunctional bimolecular toolbox. Target recognition by CRISPR-Cas systems strictly follows the Watson-Crick base pairing principle, providing a natural interface for coupling with nucleic acids. Such integration has advanced the biosensing and bioimaging methodologies, holding great promise in basic biochemical research and clinical diagnosis. Here, we summarized the latest research progress in integrating nucleic acids with CRISPR-Cas systems for advanced biosensing and bioimaging, including nucleic acid amplification and DNA circuit-coupled CRISPR methods for molecular diagnostics, functional nucleic acid-regulated CRISPR assays for biochemical analysis, and functional nucleic acid-mediated CRISPR bioimaging. We also discussed the challenges and prospects of nucleic acid-assisted CRISPR-Cas systems in biosensing and bioimaging.