OBJECTIVE This review article discusses investigational subretinal gene therapies for retinal vascular diseases, including AVA-101, an adeno-associated viral (AAV) 2 vector expressing soluble vascular endothelial growth factor (VEGF) receptor 1, ABBV-RGX-314, an AAV8 vector expressing an anti-VEGF-A antibody fragment, and EXG102-031, an AAV8 vector expressing a recombinant protein that blocks VEGF family members and angiopoietin 2. DESIGN Review article CONCLUSION: Subretinal injection is a commonly used delivery route for investigational gene therapy agents which is theorized to provide relative immune privilege, thereby reducing the risk of inflammation, while providing high transgene expression in photoreceptors and retinal pigment epithelium. Subretinal injection of AVA-101 demonstrated safety and tolerability in Phase I and IIa trials, but failed to maintain visual acuity and control exudation. In contrast, subretinal injection of some doses of ABBV-RGX-314 have shown evidence of controlling exudation and the maintaining vision, as well as safety and tolerability, leading to two ongoing pivotal trials comparing subretinal delivery of two different doses of ABBV-RGX-314 versus intravitreal injections of 0.5mg ranibizumab or 2mg aflibercept. These preliminary results are an encouraging and welcome development in the search for efficacious, long-duration treatments for retinal vascular diseases.

中文翻译：

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用于治疗视网膜和脉络膜血管疾病的视网膜下基因疗法。


目的 本文讨论了视网膜血管疾病的研究性视网膜下基因疗法，包括 AVA-101，一种表达可溶性血管内皮生长因子 （VEGF） 受体 1 的腺相关病毒 （AAV） 2 载体，ABBV-RGX-314，一种表达抗 VEGF-A 抗体片段的 AAV8 载体，以及 EXG102-031，一种表达阻断 VEGF 家族成员和血管生成素 2 的重组蛋白的 AAV8 载体。设计评论文章结论： 视网膜下注射是研究性基因治疗药物常用的递送途径，理论上可提供相对免疫特权，从而降低炎症风险，同时在光感受器和视网膜色素上皮中提供高转基因表达。AVA-101 视网膜下注射在 I 期和 IIa 期试验中显示出安全性和耐受性，但未能维持视力和控制渗出。相比之下，某些剂量的 ABBV-RGX-314 视网膜下注射已显示出控制渗出和维持视力以及安全性和耐受性的证据，导致两项正在进行的关键试验，比较两种不同剂量的 ABBV-RGX-314 的视网膜下注射与玻璃体内注射 0.5mg 雷珠单抗或 2mg 阿柏西普。这些初步结果是在寻找有效的长期视网膜血管疾病治疗方法方面令人鼓舞和受欢迎的进展。