Table 2.

An overview of preclinical research seeking to address the vasopermeability and angiogenesis aspects of DR.

Reference	Vector type	Promoter	Transgene	Target
Tu et al. [133]	scAAV2	CMV	CAD180 and CAD112	Calrectulin signaling
Wu et al. [134]	AAV5	ICAM2	SpCas9 for VEGF-RII	VEGF signaling
Huang et al. [135]	AAV1	ICAM2	SpCas9 for VEGF-RII	VEGF signaling
Díaz-Lezama et al. [136]	AAV2	CMV	Vasoinhibin and sFlt-1	VEGF signaling
Biswal et al. [137]	scAAV2	GFAP	Endostatin	Endothelium
Haurigot et al. [138]	AAV2	CAG	PEDF	VEGF signaling
Pechan et al. [130]	AAV2	CMV	sFLT-1	VEGF signaling
Jiang et al. [139]	Lipofectamine	n/a	HIF1a and VEGF siRNA	HIF1a and VEGF signaling
Lamartina et al. [131]	Adenovirus	CMV/IRES-M2	sFLT-1	VEGF signaling
Ideno et al. [132]	AAV2/5	CMV	sFLT-1	VEGF signaling
Le Gat et al. [140]	Adenovirus	CMV	ATF, endostatin	uPA/uPAR signaling
Igarashi et al. [141]	Lentivirus	CAG	Angiostatin	Endothelium
Gehlbach et al. [129]	Adenovirus	CMV	sFLT-1	VEGF signaling
Auricchio et al. [142]	AAV1/2	CMV	PEDF, TIMP3, endostatin	Endothelium

ICAM2: Intracellular adhesion molecule 2; SpCas9: Streptococcus pyogenes Cas9 CRISPR system; scAAV2: self-complementary AAV2; GFAP: glial fibrillary acidic protein; sFLT-1: soluble FLT-1 (aflibercept); ATF: amino terminal fragment; uPA/uPAR: urokinase receptor; TIMP3: inhibitors of metalloproteinases; CAG: promoter sequence incorporating cytomegalovirus (CMV) enhancer elements and chicken β-actin promoter sequences; PEDF: pigment epithelium-derived factor; HIF1ɑ: hypoxia inducible factor alpha; ATF: activating transcription factor; IRES-M2: internal ribosome entry site. Adapted from Pharmacology & Therapeutics, Vol 173, Wang et al., Gene therapy for diabetic retinopathy: Are we ready to make the leap from bench to bedside?, Copyright 2017, with permission from Elsevier [7].