Table 2:

Summary of the different Cas9 variants and their roles for the improvement of this technology.

Date	Cas variants		Purpose	Improvements	Reference
2013	WT Cas9	native Cas9(spCas9)	genome editing	specific genome editing in eukaryotic cell	16-18
2016		e-SpCas9	increase the specificity of Cas9	mutations in non-catalytic domain and reduced off-target effects	70
2016		HF1-SpCas9			71
2017		hypa-spCas9			72
2018		xCas9	expand the PAM recognition	broad range of PAM sequence and greater DNA sensitivity	73
2015		saCas9	Cas9 alternative in other organisms	smaller Cas9 with different PAM	74
2015	other major Cas molecules	Cas12a(Cpf1)	finding Cas9 alternative	smaller Cas9, easy to pack in virus	75
2016		Cas13a(C2c2)		ability to modify RNA sequence	76, 77
2018		Cas14		ability to target ss DNA	78
	mutated spCas9	fused domains
2013	Cas9n(nickease) (one mutation)	-	genome editing	reduce the chance of random double strand cut	79
2016		Cytidine Deaminase	base editing (C to T)	genome editing without ds DNA cut and donor DNA	23
2017		Deoxyadenosine deaminase	base editing (A to G)		80
2019		Reverse Transcriptase	prime editing		24
2013	dCas9 (death or inactive Cas9) (double mutation)	KRAB	gene regulation	site specific gene silencing	81
2013		VP64,VPR		site specific gene activation	82, 83
2014		Fokl	reduce off-target effect	less off-target activities	84
2015		p300	epigenome editing	site specific acetylation of H3K27	85
2016		Tet	epigenome editing	site specific removal of methyl group	86
2017		DNMT3a	epigenome editing	site specific addition of methyl group	87
2017		GFP	live-cell imaging	specific loci labeling in vivo	88
2017		PYL1,ABI1	reorganizing chromatin architecture	locus specific chromatin looping	89
2019		EZH2	epigenome editing	site specific methylation of H3K27	90