Targeting Herpetic Keratitis by Gene Therapy

Table 1

Chronologic order	Vector	Gene	Host	Rout of administration	Results and reference
1990	Vaccina virus	gD	Rabbits	Intradermal injection	No effect on herpes simplex keratitis during 16 days postinfection [99]
1997	Plasmid DNA	IL-10, IL-2, GM-CSF	Mice	Topical or intramuscular	Topical: IL-10, only, reduced lesion severity. Intramuscular: no effect [100]
1998	Plasmid DNA	IL-2, IL-4, IL-10, IFN-γ	Mice	Topical	IL-4 or IL-10: reduced lesion severity 25 days post-infection; IL-2 or IFN-γ: no effect [101]
	Plasmid DNA	IL-2, IL-4, IL-10	Mice	Topical, nasal, or intramuscular	Topical administration of IL-4 or IL-10 lowered lesion severity 21 days after infection [102]
1999	Plasmid DNA	IFN-α1	Mice	Topical	Increased survival if treated 1 day pre-infection [69]
2000	Plasmid DNA	gB1	Rabbits	Subconjunctival or intramuscular injection	Complete survival and reduction of lesions following intramuscular administration only [103]
	Plasmid DNA	gD, gD-IL-2	Mice	Subconjunctival injection	Good survival for grafts and prevention of stromal, but not epithelial, keratitis [104]
	Plasmid DNA	IFN-α1	Mice	Topical, nasal, or vaginal administration	Topical application improved the survival when treated 1 day before infection [105]
	Plasmid DNA	IFN-β	Mice	Topical	Increased survival only when applied 1 day before infection [106]
	Plasmid DNA	IFN-α1	Mice	Topical	Increased survival only when applied 12 hours before infection [107]
2001	Plasmid DNA	IFN-α1	Mice	Topical	Increased survival [108]
	Plasmid DNA	gB	Mice	Mucosal	Increased INF-γ [109]
2002	Plasmid DNA	gD-IL-2	Mice	Subconjunctival injection	Complete prevention of stromal, but not epithelial, keratitis 10 days after infection [110]
	Plasmid DNA	gD-IL-2	Mice	Topical conjunctival	Complete prevention of stromal, but not epithelial, keratitis [111, 112]
	Plasmid DNA	IL-12, IP-10	Mice	Topical	Suppression of lesions using both transgenes. IP-10, but not IL-12, suppressed lesions [113]
2003	Antisense oligonucleotides	TNF-α	Mice	Subepithelial injection	Reduction of herpes simplex keratitis signs 14 days after infection [114]
	HSV-1	IL-2, IL-4, IFN-γ	Mice	Intraperitoneal injection	All transgenes: complete survival and prevention of corneal scarring 28 days after infection [115]
2004	Plasmid DNA	gB, gC, gD, gE and gI	Mice	Intramuscular injection	Complete survival and prevention of corneal scarring 28 days after infection [116]
	siRNA duplexes with or without TargeTran	VEGF	Mice	Subconjunctival or intravenous injection	Subconjunctival or systemic administrations suppressed lesions 10 days after infection [117]
2005	HSV-1	IL-12p35, IL-12p40	Mice	Intraperitoneal injection	Both transgenes: complete survival and prevention of corneal scarring 28 days after infection [118]
	Plasmid DNA	IL-18	Mice	Topical	Suppression of lesions 12–21 days post-infection [70]
	Plasmid DNA encoding shRNA	Matrix metalloproteinase-9	Mice	Intrastromal injection	Suppression of lesions during 21 days after infection [119]
2008	siRNA	TNF-α	Mice	Intraperitoneally	Inhibition of TNF-α [120]
	Plasmid DNA	IL-10	Mice	Topical	Modulate the inflammation severity [121]
2009	Plasmid DNA	VEGFR2 VEGFR3	Mice	Subconjunctival injection	Control vascularisation after HSV-1 infection [72]
2010	Nanoparticles	IL-21 and gD vaccine	Mice	Ocular mucosal administration	Inhibits ocular HSV-1 [122]
	DNA plasmid	B and T lymphocyte attenuator	Mice	Intraperitoneal injection	Decreased CD4^+ T mediated cell response [123]

Abbreviations—gD: HSV-1 glycoprotein D; GM-CSF: granulocyte-macrophage colony-stimulating factor; INF: interferon; IL: interleukin; IP-10: IFN-inducible protein 10; shRNA: short hairpin RNA; siRNA: small interfering RNA; TNF: tumour necrosis factor; VEGF: vascular endothelial growth factor. Table updated from [124].