The CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing technology is an emerging RNA-guided nuclease system initially identified from the microbial adaptive immune systems.

In recent years, the CRISPR system has been reprogrammed to target specific regions of the eukaryotic genome and has become a powerful tool for genetic engineering. Researchers have explored many approaches to improve the genome editing activity of the CRISPR–Cas system and deliver its components both ex vivo and in vivo.

Moreover, these strategies have been applied to genome editing in preclinical research and clinical trials. In this review, we focus on representative strategies for regulation and delivery of the CRISPR–Cas system, and outline current therapeutic applications in their clinical translation.