Wozar Fabian, Seitz Immanuel, Reichel Felix, Fischer M Dominik
University Eye Hospital, University Hospital Tübingen Centre of Ophthalmology, Tübingen, Germany.
Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom of Great Britain and Northern Ireland.
Klin Monbl Augenheilkd. 2022 Mar;239(3):270-274. doi: 10.1055/a-1777-5033. Epub 2022 Feb 21.
Gene therapy is a treatment concept that uses, in most cases, viral vectors to deliver a therapeutic transgene to target cells. Although the idea of gene therapy dates back over 50 years ago, due to the complexity of the treatment concept, it took until the last decade for the responsible agencies like FDA and EMA to recommend the first gene therapy products for clinical use. The development of these therapies relies on molecular engineering of specifically designed vectors and models to test the effectiveness and safety of the treatment. Despite an increasing effort to find effective surrogates, animal models are still irreplaceable in gene therapy development. Rodents are important for exploring pathways and disease mechanisms and identifying potential treatment targets. However, only the primate eye resembles the human eye to a degree where most structures are nearly identical. Some research questions can therefore only be answered using a nonhuman primate (NHP) model. In this review, we want to summarize these key features and highlight the importance of the NHP model for gene therapy development in ophthalmology.
基因治疗是一种治疗理念，在大多数情况下，它使用病毒载体将治疗性转基因传递到靶细胞。尽管基因治疗的想法可以追溯到50多年前，但由于治疗理念的复杂性，直到过去十年，像美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）这样的负责机构才推荐首批基因治疗产品用于临床。这些疗法的开发依赖于专门设计的载体的分子工程和用于测试治疗有效性和安全性的模型。尽管人们越来越努力寻找有效的替代物，但动物模型在基因治疗开发中仍然是不可替代的。啮齿动物对于探索途径和疾病机制以及识别潜在治疗靶点很重要。然而，只有灵长类动物的眼睛在一定程度上与人类眼睛相似，大多数结构几乎相同。因此，一些研究问题只能使用非人类灵长类动物（NHP）模型来回答。在这篇综述中，我们想总结这些关键特征，并强调NHP模型在眼科基因治疗开发中的重要性。
