Designer nucleases to treat malignant cancers driven by viral oncogenes

Table 2 Targeted nucleases to oncogenic viruses

Viral target	Modality	Target	Cell lines	In vivo	Vector	Delivery method	Reference
HPV	spCas9 or dspCas9-FokI	E6, E7, LCR	SiHa	Yes	Plasmid DNA	No	[27, 111]
		E6, E7	Hela, SiHa	No	Plasmid DNA	No	[28]
		E7	SiHa, CaSki	No	Plasmid DNA	No	[30]
		E6	Hela, HSC-2, SKG-I	Yes	AAV genome	AAV-2^a (intratumoral)	[32]
		E6, E7	Hela, CaSki	Yes	Plasmid DNA	‘Stealth’ Liposomes (Intravenous)	[37]
		E6, E7	Hela	No	Plasmid DNA	No	[47]
		E6, E7	SCC2	No	Plasmid DNA	No	[33]
	TALEN	E6, E7	SiHa, S12, Hela	Yes	Plasmid DNA	Cationic polymer (Topical)	[35]
	TALEN	E7	SiHa, CaSki	No	Plasmid DNA	No	[48, 49]
	ZFN	E7	SiHa, Hela, CaSki, S12	Yes	Plasmid DNA	Cationic polymer (Intratumoral)	[36]
	BEF	LCR	Hela	No	Plasmid DNA	No	[38]
	AZP-SNase or scFokI	LCR	None	No	Plasmid DNA, Protein	No	[39,40,41, − 42, 46]
HTLV-1	ZFN	LTR	C8166, S1T, ED	Yes	Plasmid DNA	No	[67]
EBV (HHV-4)	spCas9	EBNA-LP, 125 bp repeat, EBNA3C, EBNA1, pstI repeat, LMP1	Raji	No	Plasmid DNA	No	[78]
		EBNA1, oriP, miRNA promoter	SNU-719	No	Lentiviral vector	No	[79]
		LMP1	EBV infected cell line	No	Plasmid DNA	No	[87]
		EBNA1, oriP and W repeats	C666-1	No	Plasmid DNA	No	[80]
	TALEN	EBNA1	Raji, SNU-719, SNU-265	No	Plasmid DNA	No	[77]
KSHV (HHV-8)	spCas9	LANA	Vero219, L1T2, BC3	No	Adenoviral genome	Replication-deficient Ad5 (Intratumoral)	[84]
KSHV (HHV-8)	spCas9	K12-miR promoter miR-K12-1 miR-K12-9	BCP-1, BCBL-1	No	Plasmid DNA	No	[90]
MCPyV	spCas9	LT and sT	MS-1, WaGa	No	Plasmid DNA	No	[106]

The modalities that have been developed against their respective oncogenic viruses and targets in each study are shown. The in vitro cell lines as well as whether in vivo studies were performed are highlighted. The delivery vectors developed are indicated along with the route of administration used in vivo. The expression vector used for the different nuclease modalities are indicated
^aAAV delivered gRNA to Cas9 overexpressing cell line

ISSN: 1743-422X