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Anti-VEGF intravitreal injections are effective in treating wet age-related macular degeneration (AMD). However, longer-lasting anti-VEGF agents are needed to reduce the burden associated with intravitreal injections. This study, published in Investigative Ophthalmology & Visual Science, sought to evaluate the use of non-viral gene therapy to treat choroidal neovascularization (CNV) in rats using the anti-VEGF agent aflibercept or Decorin, an endogenous TGF-beta inhibitor.

The researchers designed a novel dual-gene plasmid, EYS809, to deliver both proteins. Transfer of aflibercept or Decorin was done through electrotransfer into the rat ciliary muscle three days before laser-induced CNV. Intravitreal injection of aflibercept or recombinant Decorin served as positive controls. CNV leakage was assessed with fluorescein angiography. 

Ultimately, it was found that plasmid administration of aflibercept reduced Grade 3 CNV lesions to 11%, while intravitreal administration of aflibercept reduced them to 29%, compared to 59% in untreated rats. Similarly, plasmid administration of Decorin reduced Grade 3 CNV lesions to 36%, while intravitreal administration of Decorin reduced them to 24%, compared to 59% in untreated rats. 

The researchers concluded that their non-viral gene therapy method of sustained anti-VEGF delivery is viable as an alternative to repeated intravitreal injections. Moreover, they asserted that the combined effect of aflibercept and Decorin expressed from EYS809 could provide better results than aflibercept alone [1]. 

Source:

[1] Orhan, E., Bigot, K., Gondouin, P., Bénard, R., Piazza, M., Buggage, R., Behar-Cohen, F. F., & Bordet, T. (2021). EYS809 non-viral gene therapy to improve convenience and outcomes in wet AMD. Investigative Ophthalmology & Visual Science, 62, 228. https://iovs.arvojournals.org/article.aspx?articleid=2772991

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