Targeting vascular endothelial growth factor using retinal gene therapy.
Targeting vascular endothelial growth factor using retinal gene therapy.
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DOI：
10.21037/atm-20-4417
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发表时间：
2021-08
影响因子：
--
通讯作者：
Yiu G
中科院分区：
文献类型：
--
作者：
Chung SH;Frick SL;Yiu G
针对血管内皮生长因子(VEGF)的药物治疗已经彻底改变了新生血管视网膜疾病的治疗方法，包括糖尿病视网膜病变和新生血管老年性黄斑变性。然而，一些患者的频繁注射、高昂的费用和治疗耐药性的负担仍然没有解决。为了克服这些挑战，目前正在开发新一代的抗血管生成生物疗法、工程蛋白质、植入性给药系统和生物聚合物，以实现更持久、更持久的治疗。自从FDA首次批准了一种用于治疗与双等位基因RPE65突变相关的遗传性视网膜疾病的基因疗法以来，使用基因疗法治疗病理性血管生成重新引起了人们的兴趣。新一代的病毒载体和新颖的眼内注射方法有助于克服眼部障碍，提高转导效率和安全性。此外，与目前采用生物工厂方法来模仿现有药物疗法的抗血管内皮生长因子基因治疗策略不同，在DNA水平上针对促血管生成因子的新型基因组编辑策略提供了一种独特而独特的机制方法，可能更精确，并可能导致根治。本文综述了目前抗血管内皮生长因子的治疗方法和正在开发的新的药理药物，综述了抗血管内皮生长因子基因治疗的技术和进展，并探讨了CRISPR-Cas9技术在抑制眼血管生成方面的应用前景。
Pharmacotherapies targeting vascular endothelial growth factor (VEGF) have revolutionized the management for neovascular retinal disorders including diabetic retinopathy and neovascular age-related macular degeneration. However, the burden of frequent injections, high cost, and treatment resistance in some patients remain unresolved. To overcome these challenges, newer generations of anti-angiogenic biological therapies, engineered proteins, implantable delivery systems, and biopolymers are currently being developed to enable more sustained, longer-lasting treatments. The use of gene therapies for pathologic angiogenesis has garnered renewed interests since the first FDA-approval of a gene therapy to treat inherited retinal diseases associated with biallelic RPE65 mutations. Newer generations of viral vectors and novel methods of intraocular injections helped overcome ocular barriers, improving the efficiency of transduction as well as safety profile. In addition, unlike current anti-VEGF gene therapy strategies which employ a biofactory approach to mimic existing pharmacotherapies, novel genome editing strategies that target pro-angiogenic factors at the DNA level offer a unique and distinct mechanistic approach that can potentially be more precise and lead to a permanent cure. Here, we review current anti-VEGF therapies and newer pharmacologic agents under development, examine technologies and progress in adapting anti-VEGF gene therapies, and explore the future application of CRISPR-Cas9 technology to suppress ocular angiogenesis.
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