Gene therapy in neovascular age related macular degeneration: an update.

IF 2.4 3区医学 Q2 OPHTHALMOLOGY

Graefe’s Archive for Clinical and Experimental Ophthalmology Pub Date : 2025-04-28 DOI:10.1007/s00417-025-06837-2

Erika Quesada, Sofía Rojas, Xiomara Campos, Lihteh Wu

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引用次数: 0

Abstract

Neovascular age-related macular degeneration (NV-AMD) is a leading cause of preventable blindness in the elderly. Intravitreal injections of anti-VEGF agents are currently the treatment of choice for NV-AMD. However this treatment is burdensome and fosters non-compliance which leads to inferior visual outcomes. Gene therapy has emerged as a promising therapeutic option for NV-AMD that may improve these outcomes. Potential risks of gene therapy include a potential immune response that may be elicited by the vector, accidental activation of oncogenes or inactivation of tumor suppresor genes leading to malignant transformation via insertational mutagenesis and integration of the viral DNA inserts into the host's DNA. The main strategy of current gene therapy for NV-AMD has focused on delivering transgenes that express anti-angiogenic proteins that directly or indirectly inhibit the VEGF pathway. Ixoberogene soroparvovec, RGX-314 and 4D-150 are the leading NV-AMD genetic treatment programs. Pre-clinical models suggest that genome surgery with clustered regularly interspaced short palindromic repeats (CRISPR) may be another option in the future.

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新血管性年龄相关性黄斑变性的基因治疗：最新进展。

新生血管性年龄相关性黄斑变性（NV-AMD）是老年人可预防性失明的主要原因。玻璃体内注射抗vegf药物是目前NV-AMD的治疗选择。然而，这种治疗是繁重的，并促进不遵守，导致较差的视力结果。基因治疗已成为一种有希望的治疗选择，可以改善这些结果。基因治疗的潜在风险包括可能由载体引发的潜在免疫反应，致癌基因的意外激活或肿瘤抑制基因的失活，通过插入性突变和病毒DNA插入物整合到宿主DNA中导致恶性转化。目前NV-AMD基因治疗的主要策略集中在传递表达直接或间接抑制VEGF通路的抗血管生成蛋白的转基因。Ixoberogene sorparvovec、RGX-314和4D-150是领先的NV-AMD基因治疗项目。临床前模型表明，使用聚集规律间隔短回文重复序列（CRISPR）的基因组手术可能是未来的另一种选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Graefe’s Archive for Clinical and Experimental Ophthalmology 医学-眼科学

CiteScore

5.40

自引率

7.40%

发文量

398

审稿时长

3 months

期刊介绍： Graefe''s Archive for Clinical and Experimental Ophthalmology is a distinguished international journal that presents original clinical reports and clini-cally relevant experimental studies. Founded in 1854 by Albrecht von Graefe to serve as a source of useful clinical information and a stimulus for discussion, the journal has published articles by leading ophthalmologists and vision research scientists for more than a century. With peer review by an international Editorial Board and prompt English-language publication, Graefe''s Archive provides rapid dissemination of clinical and clinically related experimental information.