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
Publication Date
2021-06-24
Document Type
Article
Disciplines
Eye Diseases | Genetics and Genomics | Ophthalmology | Therapeutics
Abstract
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.
Keywords
anti-VEGF, corneal neovascularization, gene therapy, recombinant adeno-associated virus
Rights and Permissions
Copyright 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
10.1016/j.omtm.2021.06.007
Source
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
Related Resources
PubMed ID
34514023
Repository Citation
Su W, Sun S, Tian B, Tai PW, Luo Y, Ko J, Zhan W, Ke X, Zheng Q, Li X, Yan H, Gao G, Lin H. (2021). Efficacious, safe, and stable inhibition of corneal neovascularization by AAV-vectored anti-VEGF therapeutics. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.omtm.2021.06.007. Retrieved from https://escholarship.umassmed.edu/oapubs/4808
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Eye Diseases Commons, Genetics and Genomics Commons, Ophthalmology Commons, Therapeutics Commons