Table 2.

The cascade contribution in the CRISPR system.

Years	Findings	Bibliography
1987	Discovery of the CRISPR clustered repeats	[38]
2000	Acceptance of the widespread presence of CRISPR families in prokaryotes	[39]
2002	The Cas gene was discovered and given the name “CRISPR.”	[34]
2005	Adaptive immunity function was proposed, and foreign origins of spacers were identified using PAM	[40]
2007	First experimental proof that CRISPR conferred adaptive immunity	[41]
2008	CRISPR acts upon DNA target	[42,43]
	Discovered the function of crRNA
2009	Cleavage of RNA by Type III B Cmr CRISPR complex	[44]
2010	Cleavage of target DNA via DSBs through Cas9 was guided by spacer sequences	[45]
2011	Discovery of tracrRNA in conjunction with Cas9 that formed a duplex structure with crRNA	[45]
2012	Characterization of Cas9’s DNA targeting in vitro	[46]
2013	Mammalian cell genome editing for the first time	[47]
	Discovery of dCas9, CRISPRi, and CRISPRa
2014	Crystal structure of Cas9 in guide RNA and target DNA, genome-wide functional screening with Cas9, and crystal structure of apo-cas9	[48,49,50]
2015	CRISPR/Cas9 was used to edit human embryos but with prominent off-target effects, CRISPR/Cas9 was used to develop virus-resistant tomato plants, and discovery of Cas 12a (Cpf1)	[51,52]
2016	The invention of base editor (BE)	[53]
	Discovery of Cas13a (C2c2)
2019	The invention of nCATS by CRISPR/Cas9	[54]
2020	Discovery of the vfCRISPR	[55]

PAM: protospacer adjacent motif. crRNA: CRISPR/RNAs. tracrRNA: transactivating CRISPR RNA. Cmr: CRISPR RAMP module. dCAS: dead CAS system 9. CRISPRi: CRISPR interference. CRISPRa: CRISPR activation.