TABLE 1.

Cas effector protein variants and orthologs with potential for use in targeting HIV-1.

Type	Effector/Name	Size (aa)	Spacer (nt)	PAM/PFS	Target	DSB	HIV-1 target	Host target	Ref.
II-A	SpCas9	1,368	20	5'-(PS)-NGG	dsDNA	Blunt	Ebina et al. (2013), Hu et al. (2014), Liao et al. (2015), Zhu et al. (2015), Wang et al. (2016a), Kaminski et al. (2016b), Wang et al. (2016b), Kaminski et al. (2016c), Wang et al. (2016c), Yin et al. (2016), Lebbink et al. (2017), Ophinni et al. (2018), Chung et al. (2020), Ophinni et al. (2020), Sessions et al. (2020), Herskovitz et al. (2021), Khanal et al. (2022), Allen et al. (2023)	CCR5/CXCR4 (Li et al., 2015; Liu et al., 2017c; Ehrke-Schulz et al., 2017; Xu et al., 2017; Knipping et al., 2022; Li et al., 2022; Scheller et al., 2022)	Cong et al. (2013), Hsu et al. (2013), Mali et al. (2013), Ran et al. (2013), Nishimasu et al. (2014), Wu et al. (2014)
								APOBEC3G/APOBEC3B (Bogerd et al., 2015)
								Tetherin (Zhang et al., 2019b)
II-A	SpCas9-NG	1,368	20	5’-(PS)-NG	dsDNA	Blunt	-	CCR5/CXCR4 (Knipping et al., 2022)	Nishimasu et al. (2018), Kim et al. (2020), Oura et al. (2021), Sangree et al. (2022)
II-A	SaCas9	1,053	21–23	5'-(PS)-NNGRRT	dsDNA	Blunt	Kaminski et al. (2016a), Yin et al. (2017), Wang et al. (2018), Dash et al. (2019)	CCR5/CXCR4 (Wang et al., 2017; Xiao et al., 2019a; Dash et al., 2023)	Nishimasu et al. (2015), Ran et al. (2015)
II-A	SaCas9-KKH	1,053	20–23	5'-(PS)-NNNRRT	dsDNA	Blunt	-	CCR5 (Liu et al., 2021a)	Kleinstiver et al. (2015a), Yuen et al. (2022)
V-A	LbCas12a (Cpf1)	1,228	23–25	5′-TTTV-(PS)	dsDNA; ssDNA	5′ staggered	Gao et al. (2020), Fan et al. (2022), Krysler et al. (2022)	-	Dong et al. (2016), Yamano et al. (2017), Chen et al. (2018)
V-A	AsCas12a (Cpf1)	1,307	24	5′-TTTN-(PS)	dsDNA; ssDNA	5′ staggered	Liu et al. (2021b)	CCR5 (Liu et al., 2020)	Yamano et al. (2016), Yamano et al. (2017), Chen et al. (2018)
V-B	AaCas12b (C2c1)	1,129	20	5′-TTN-(PS)	dsDNA	5′ staggered	-	CCR5 (Teng et al., 2018)	Shmakov et al. (2015), Teng et al. (2018)
V-E	Cas12e (PlmCasX2)	978	16–24	5′-TTCN-(PS)	dsDNA	5′ staggered	-	CCR5 (Armstrong et al., 2023)	Burstein et al. (2017), Liu et al. (2019), Yang and Patel (2019), Selkova et al. (2020)
VI-A	LbuCas13a (C2c2)	1,159	24	No PFS requirement	ssRNA	N/A	Yin et al. (2020)	-	Liu et al. (2017b)
VI-D	RspCas13d (CasRx)	922	20	No PFS requirement	ssRNA	N/A	Nguyen et al. (2021)	-	Konermann et al. (2018), Yan et al. (2018), Zhang et al. (2018), Zhang et al. (2019a), Cheng et al. (2023)

N/A, not applicable; nt, nucleotide(s); aa, amino acids; PAM, protospacer adjacent motif; PFS, protospacer flanking sequence PS, protospacer; N, any base; R = A/G; Y = C/T; W = A/T;V = A/C/G; H = A/C/T; D = A/G/T; M = A/C; B = G/T/C.