Timeline of CRISPR Evolution: From DNA Editing to Applications in Precision Oncology. (IMAGE)
Caption
This figure illustrates the evolution of CRISPR technology from 1987 to 2019, presented in a horizontal timeline format and categorized into four generations, each denoted by a distinct color: The first generation (blue) represents DNA double-strand break editing technology, initiated with the establishment of the SpCas9 system in 2007 and subsequently refined for precision through advances such as the Cas9-D10A nickase and the high-fidelity SpCas9-HF1 in 2015; The second generation (orange) refers to targeted DNA cutting technology, including Cas12, developed in 2015, and Cas14, invented in 2018, which overcame PAM sequence restrictions, thereby enabling a broader target range and expanding applications from gene editing to molecular-level diagnostics; The third generation (green) involves targeted RNA regulation technology, encompassing the CRISPRi/a system for transcriptional regulation, the Cas13 system, invented in 2016, for the specific degradation and modification of cancer-related mRNA, and dCas9-DNMT3A/TET1-mediated DNA methylation editing developed between 2022 and 2023; The fourth generation (yellow) encompasses precise editing technologies that avoid double-strand breaks, including base editors (CBE/ABE), developed in 2016, and the Prime Editor, introduced in 2019, which have broadened applications to include the repair of diverse point mutations and the correction of tumor driver genes such as EGFR.
Credit
Kailai Li，Peixin Huang，Yue Qian，Anqi Lin，Jingjun He，Junyi Shen，Li Chen，Kai Miao，Jian Zhang
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