Table 1.

Comparison of the different Cas9 functions that have been successfully demonstrated.

Function	Cas9 variant	Effector domain	sgRNA target	Detection method	Reference
Knockout and Knockin	WT nickase	– –	ORF	HRM; IDAA; Mismatch endonuclease;	Cong et al., 2013; Jinek et al., 2013; Mali et al., 2013a
	dCas9	Fok I		PAGE; Western blot; Sanger Sequencing;	Guilinger et al., 2014; Tsai et al., 2014
Activation	dCas9	Multimers of VP16 (VP48, VP64, VP160) p65 SunTag	Promoter	RT-PCR Western blot	Cheng et al., 2013; Gilbert et al., 2013; Maeder et al., 2013; Mali et al., 2013a; Tanenbaum et al., 2014; Konermann et al., 2015
Silencing	dCas9	KRAB	Promoter	RT-PCR Western blot	Larson et al., 2013; Qi et al., 2013; Gilbert et al., 2014
Gene tagging	dCas9	GFP/SunTag	Any	Immunostaining Microscopy Western blot	Tanenbaum et al., 2014
Genome locus visualization	dCas9	BFP EGFP GFP, 3xGFP, mCherry	Any	Microscopy	Chen et al., 2013; Ma et al., 2015
Optogenetic activation	dCas9	CIB1/CRY2	Promoter	Variable	Nihongaki et al., 2015; Polstein and Gersbach, 2015
Split reporter	Split Cas9	–	Any	Variable	Truong et al., 2015; Wright et al., 2015

ORF, open reading frame; HRM, high-resolution melt analysis; IDAA, indel detection by amplicon analysis; PAGE, poly-acrylamide electrophoresis; VP16, tegument protein VP16 of herpes simplex virus; SunTag, peptide array that recruites multiple copies of an antibody fusion protein and GFP; KRAB, Kruppel associated box; EGFP, enhanced green fluorescent protein; BFP, blue fluorescent protein; CIB1, calcium and integrin binding 1; CRY2, cryptochrome circadian clock 2.