Fig. 1

Timeline of major events in the development of CRISPR/Cas technology and representative Cas9 variants. In 1987, the CRISPR sequence was first reported. The mechanism by which Cas9 cuts DNA double strands was reported in 2012, and Cas9 was subsequently used for gene editing in mammalian cells. Since then, CRISPR technology has developed rapidly, and multiple Cas9 variants with specific functions have been identified. The representative variants are single-base substitution tools (e.g., CBE and PE) and transcriptional regulatory tools (e.g., dCas9-effector). Since 2016, CRISPR-based gene-editing technologies have been successively used in clinical treatment with great success. CRISPR clustered regularly interspaced short palindromic repeats, Cas CRISPR-associated, dCas9 dead Cas9, PAM protospacer-adjacent motifs, CBE cytosine base editors, ABE adenine base editors, GBE glycosylase base editors. (Figure was created with Adobe Illustrator)