Molecular reporters for CRISPR/Cas: From design principles to engineering for bioanalytical and diagnostic applications

CRISPR/Cas machinery has revolutionized the analytical platform for the precise detection of diverse analytes. Specific target recognition and robust signal transduction are crucial requirements for a superior sensing platform. The signal generation is directly related to the reporter traits in CRISPR/Cas systems. This review illustrated reporter engineering and its significance in improving the CRISPR/Cas-based detection platform. It is the first review highlighting the role of reporter elements, the nucleic acid sequence and transducer, for multiplexing and discriminate detection of targets. We described the significance of the reporters, the role of Cas ribonucleoproteins and their specific reporters, reporter nucleic acid and transducer engineering and their impact on multiplexing and target differentiation, working principles of reporters, demerits of CRISPR technology, and upcoming investigation. We envision that this review will be a milestone in fabricating the CRISPR/Cas reporters and discriminate multiplexed sensors for applications on a commercial scale. •The critical roles of reporters in CRISPR/Cas-based bioassays are specified.•The design principles of CRISPR/Cas reporters are discussed.•The strategies for reporter engineering are described.•The limitations of current reporters and perspectives of future horizons are critically discussed.