UMMS Affiliation

Department of Ophthalmology and Visual Sciences; Horae Gene Therapy Center; Department of Microbiology and Physiological Systems; Viral Vector Core; Li Weibo Institute for Rare Diseases Research

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Document Type



Eye Diseases | Genetics and Genomics | Ophthalmology | Therapeutics


Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8-KH902 far exceeded that of rAAV2-KH902. A single-dose rAAV8-KH902 treatment at 8 x 10(8) genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10-14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8-KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV.


anti-VEGF, corneal neovascularization, gene therapy, recombinant adeno-associated virus

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Copyright 2021 The Authors. This is an open access article under the CC BY license (

DOI of Published Version



Su W, Sun S, Tian B, Tai PWL, Luo Y, Ko J, Zhan W, Ke X, Zheng Q, Li X, Yan H, Gao G, Lin H. Efficacious, safe, and stable inhibition of corneal neovascularization by AAV-vectored anti-VEGF therapeutics. Mol Ther Methods Clin Dev. 2021 Jun 24;22:107-121. doi: 10.1016/j.omtm.2021.06.007. PMID: 34514023; PMCID: PMC8413663. Link to article on publisher's site

Journal/Book/Conference Title

Molecular therapy. Methods and clinical development

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.