Engineering molecular switches of CRISPR/Cas12a for biosensing applications

Benefiting from high specificity, excellent programmability, and efficient signal amplification capability, the CRISPR/Cas12a system has emerged as a crucial tool in the field of molecular diagnostics. To fully realize the application potential of Cas12a, many molecular switches of CRISPR/Cas12a have been recently developed to convert the activity of Cas12a from an inactive state to an active state in response to external stimuli, which significantly improves the biosensing performance in terms of the sensitivity, selectivity, and accuracy. This review summarizes recent progress in the development and application of Cas12a-based molecular switches, with a focus on their conditional activation mechanisms and biosensing applications. Additionally, challenges and future perspectives for the development of intelligent biosensors are discussed.