Table 2.

AAV gene therapy for treatment of corneal neovascularization.

Target gene	Virus serotype	Delivery	Subject	Model	Dose	Follow-up duration	Result	Serious side effect
Decorin [85]	rAAV5	Topical(with epithelium removed)	Rabbit	Implant VEGF pellet into cornea stroma pocket	A single topical AAV5 titer (100 μl; 5 × 1012 vg/ml) (one day after VEGF pellet implantation)	2 weeks	Significant reduction in corneal neovascularization by 63 ± 6.3% on day 14, with no major side effects	None
Decorin [67]	rAAV5	Topical apply	Rabbit	—	50 μl titer; (6.5 × 1012 vg/ml)	6 months	AAV5–Dcn gene therapy caused no significant toxicity to the cornea	None
HLA-G codon [99]	rAAV8G9	Intrastromal injection	Rabbit	Alkali burn	Injection of 5 × 1010 viral genomes (seven days after corneal wounding)	8 weeks	Inhibited α-SMA expression and near complete inhibition of corneal vascularization	None
Endostatin [70]	rAAV2-CMV	Subconjunctival injection	Mice	Chemical cauterization	5 μl; 2.5 × 107 viral particles (two weeks before chemical cauterization)	8 months	Significantly inhibit of angiogenesis	None
Angiostatin [62]	rAAV	Subconjunctival injection	Rat	Alkali burn	5 μl; 1 × 1010 viral particles (three weeks before alkali injury)	16 weeks	Reduced alkali burn-induced corneal angiogenesis	None
KH902 [131]	rAAV2/rAAV8	Intrastromal or subconjunctival injection	Mice	Alkali burn or suture procedures	4 μl; 1.6 × 1010 genome copies (GCs)/8 × 108 GCs	12 weeks	Significantly inhibit of corneal neovascularization	None
miR-204 [133] (a microRNA)	rAAVrh.10	Intrastromal or subconjunctival injection	Mice	Alkali burn	4 μl; 3.6 × 1010 GCs	2 weeks	Partial inhibit of corneal neovascularization	None
sFlt-1 [132]	rAAV2-CMV	Intra-cameral injection	Rat	Cautery-induced	2 μl; 4 × 1011particles/ml	16 weeks	Reduced the development of corneal neovascularization by 36%	None

HLA-G: human leukocyte antigen G. Plgf1-de: a placental growth factor 1 variant, KH902Conbercept, also known as KH902, is an anti-VEGF drug, which is a soluble recombinant protein.