Rational engineering of nucleic acid probe system for enhanced intracellular MicroRNA detection

The spatial–temporal and dynamic expression profiles of intracellular microRNA (miRNA) are extremely crucial for deciphering a serial of cellular biological behaviors and monitoring pathological processes. Intensive efforts have been devoted to design nucleic acid probe systems to carry out various biological tasks in living cells, which benefits from intrinsic biosecurity, excellent biocompatibility, ease of synthesis, and amenability to functionalization. More important, given their highly efficient recognition and signal amplification ability to nucleic acid molecules via Watson-Crick base pairing-driven hybridization, they also become the best candidate tools for intracellular miRNA sensing. In this review, we highlight the recent achievements in nucleic acid probe systems, aiming to reveal how to customize intracellular miRNA analysis system with expected performance for enhanced detection, including the approaches for high sensitivity, good selectivity, and improved accuracy. The review ends with a “Conclusions and Perspectives” section highlighting the current challenges and future opportunities for nucleic acid probe systems regarding intracellular miRNA analysis.