Table 2.

CRISPR/Cas9 utilized in gene therapy.

Gene Studied	Experiment	Outcome	Significance	References
S334ter	Mutate the S334ter gene in transgenic rats; NHEJ	Mouse models for RP had improved visual function and did not demonstrate retinal degeneration	Potential for use in human clinical trials in the future	[69]
RHO	Edit RHO in vivo by electroporating CRISPR/Cas9 plasmids into transgenic mice carrying mutated human RHO; NHEJ	Transgenic mice demonstrated disrupted P23H-RHO	Demonstrates efficacy and feasibility of studying human genes in murine disease models of RP	[71]
Rho	Selective editing of mutant P23H allele in Rhodopsin; NHEJ	CRISPR-edited Rho+/P23H mice had improved retinal function and slower photoreceptor degeneration compared to controls	Proof of concept that CRISPR can target mutant allele while leaving healthy allele intact; great potential for therapy	[73]
RPGR	Create XLRP patient-specific iPSCs, then use CRISPR/Cas9 to correct the RPGR gene; HDR	iPSCs with corrected RPGR gene	Potential for future iPSC- based transplantation therapies to treat XLRP	[75]
Nrl	Knockout of Nrl in post-mitotic photoreceptors in retinas of 3 separate disease models for rod-specific gene mutations; NHEJ	Affected rods take on cone-associated characteristics; Preservation of Cone function	NRL is associated in rod cell fate even in post-mitotic photoreceptors	[59]
Mertk	Knock-in exon 2 of Mertk in RCS rat model for RP; HITI	Partial rescue of vision; Better preservation of ONL thickness and better ERG responses compared to controls	Earlier intervention time could overcome partial rescue	[76]
VEGF-A	Edit exon 1 of VEGF-A in human RPE cell line ARPE-19; NHEJ	Cell line had insertion- deletions and decreased levels of Vegf-A protein	Proof of concept shows that CRISPR/Cas9 can edit genes involved in retinal diseases more efficiently than other methods (antibodies, decoy proteins)	[79]
Vegfa	Subretinal injection of Vegfa-specific Cas9 into AMD mouse models	Experimental mice demonstrated smaller areas of CNV after laser injury compared to controls	CRISPR/Cas9 has the potential to locally treat degenerative diseases (i.e. AMD)	[77]
VEGFR2	Disrupt VEGFR2 in oxygen induced retinopathy (OIR) and laser-injury-induced choroid neovascularization (CNV) mice; NHEJ	CRISPR-edited mice had less CNV than controls	Disruption of VEGFR2 suppresses neovascularization	[80]
VEGFR2	Compare disruption of VEGFR2 in human retinal microvascular endothelial cells(HRECs) via CRISPR/Cas9 vs. aflibercept or ranibizumab; NHEJ	CRISP R-treated cells demonstrated less VEGF-stimulated activity than did aflibercept or ranibizumab-treated cells	CRISPR/Cas9 has great potential to treat patients with pathologic angiogenesis (i.e. AMD and PDR patients)	[78]
VEGFR2	CRISPR-mediated depletion of VEGFR2 in HRECs to study effects on angiogenesis; NHEJ	CRISPR-edited HRECs demonstrated characteristics of blocked angiogenesis	CRISPR-mediated depletion of VEGFR2 could lead to therapies for patients with AMD and PDR	[18]
CEP290	Creation of cellular model of LCA10 and editing of the gene to fix the splice mutation; HDR	Creation of healthy cell line	Potential to treat patients with cell line of wild-type CEP290	[81]