Gene editing for corneal disease management

Table 1 Application of gene editing for corneal disease management

Disease	Target genes for gene editing
Corneal fibrosis	BMP7, CTGF, Decorin, Hevin, Moesin, Smad2, Smad3, Smad4, Smad7, TGFβ1, TGFβR2, TRPA-1, Twist2, Vimentin
Corneal wound healing	CTGF, CNTF, EGF, EGFR1, EGFR2, Fibronectin, IGF, KGF, Laminin, Lumican, MIF, MMP-1, MMP-2, MMP-3, MMP-9, NGF, OGF, PAI-1, PAF, PDGF, rho-associated protein kinase (ROCK), TGFβ1, TGFβ2, TGFβ3, TLR4, TIMP-2, Vasohibin
Corneal neovascularization	Angiopoietin 1, Angiopoietin 2, Angiostatin, βFGF, Endostatin, FGFR-1, FGFR-2, FGFR-3, FGFR-4, FOXC1, HGF, IGF, IL-8, IL-1, Leptin, MMP-2, MMP-9, MMP-14, Netrin-1, Netrin-4, Neuropilin-2, NF-κB, PAI-1, PDGF, PEDF, PGF, Prox-1, ROCK, TNFα, TGFβ, TSP-1, Tie2, VCAM-1, VE-Cadherin, VEGF, VEGFR-1, VEGFR2, VEGFR-3
Keratoconus	BANP-ZNF469, LOX, BNIP3, CAST, CLF1, COL4A4, COL5A1, CPT1B, CPTB1B, DOCK9, IL-1A, IL-1B, IPO5, KRT72, MPDZ-NFIB, NEFL, Noxa, PMAIP1, RAB3GAP1, SLC25A2, SLC25A4, SLC25A31, SOD2, STK24, TGFB1, TIMP1, TIMP3, UCP1, UCP3, VSX1, ZEB1
Congenital hereditary endothelial dystrophy	SLC4A11
Epithelial basement membrane dystrophy	TGFBI
Francois-neetens mouchetee fleck corneal dystrophy	PIKFYVE (PIP5K3)
Fuchs' endothelial corneal dystrophy	APEX1, AGBL1, COL8A2, LOXHD1, NOX4, SLC4A11, SnaI1, TCF4, TCF8, ZEB1
Granular corneal dystrophy type 2	TGFBI, TGFBIp
Gelatinous drop-like corneal dystrophy	TACSTD2
Macular corneal dystrophy	CHST6
Meesmann epithelial corneal dystrophy	KRT3, KRT12
Posterior polymorphous corneal dystrophy	COL8A2, VSX1, ZEB1
Reis-Bücklers' and Thiel-Behnke Corneal dystrophies	TGFBI
Schnyder corneal dystrophy	UBIAD1

TGFβ1: Transforming growth factor beta 1; TGFβR1: Transforming growth factor btea receptor 2; EGF: Epifdermal growth factor; MMP-1: Matrix metalloproteinase-1; TIMP-2: Tissue inhibitor of metalloproteinases metallopeptidase inhibitor 2; TLR4: Toll-like receptor 4; IL: Interleukin; NF-κB: Nuclear factor kappa B; TNFα: Tumor necrosis factor alpha.

Table 2 Potential applications of zinc finger nucleases, transcription activator-like effector nucleases and Clustered Regularly Interspaced Short Palindromic Repeat/Clustered Regularly Interspaced Short Palindromic Repeat Associated Systems to develop novel disease models and innovative therapeutic strategies

Target gene	Target cell	ZFN/TALEN/CRISPR	Disease	Ref.
α-Globin	Human iPS	ZFN	α-thalassemia	[104]
Tnfrsf9	NOD mouse embryo	ZFN	Diabetes	[105]
HBV	Huh7 cells	ZFN	Hepatitis B	[106]
CCR5, CXCR4	CD4+ T cells	ZFN	HIV	[107]
CCR5, IL2RG	Multiple	ZFN	HIV, X-SCID	[108]
TCRα, β	T cells	ZFN	Leukemia	[109]
HBB	Human iPS cells	ZFN	Sickle cell anemia	[110]
PIG-A	Human ES, iPS cells	ZFN	PNH	[111]
gp91(phox)	Human iPS cells	ZFN	X-CGD	[112]
Albumin	Mouse hepatocytes	ZFN	Hemophilia A and B	[113]
SCN1A	Human iPS	TALEN	Epilepsy	[114]
PSIP1	HT1080, 293T, Jurkat	TALEN	HIV	[115]
HBB	Human iPS cells	ZFN/TALEN/CRISPR	Sickle cell anemia	[116]
gp91(phox)	Human iPS cells	TALEN	X-CGD	[117]
Ctnnb1, Apc	H2.35	TALEN	Hepatocellular carcinoma	[118]
hFVIII	Human iPS cells	TALEN	Hemophilia A	[119]
PLN R14del	Human iPS cells	TALEN	Cardiomyopathy	[120]
BUB1B	HCT116	TALEN	PCS (MVA)	[121]
MECP2	Monkey zygotes	TALEN	Rett syndrome	[122]
Sry, Uty	Mouse blastocysts	TALEN	NA	[123]
Dystrophin	Myoblasts	CRISPR/Cas9	DMD	[124]
FANCC	Patient fibroblasts	CRISPR/Cas9	Fanconi anemia	[125]
APC, SMAD4, TP53, KRAS, PIK3CA	Human intestinal epithelial organoids	CRISPR/Cas9	Colorectal cancer	[126]
FAH	Mouse liver	CRISPR/Cas9	Tyrosinemia	[127]
PTEN, TP53	Mouse liver	CRISPR/Cas9	Liver cancer	[128]
DMD	Mdx mouse zygotes	CRISPR/Cas9	DMD	[129]
B2M, CCR5	CD4+ T and CD34+ HSC	CRISPR/Cas9	NA	[130]
CFTR	CF intestinal organoids	CRISPR/Cas9	Cystic Fibrosis	[131]
C. parvum	HCT8	CRISPR/Cas9	Cryptosporidiosis	[132]
HCV	Huh7.5	FnCas9	Hepatitis C	[133]

ZFN: Zinc finger nuclease; TALEN: Transcription activator-like effector nucleases; CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats; Cas9: CRISPR associated protein 9; HIV: Human immunodeficiency virus; NOD: Non-obese diabetic.