With recent advances in adeno-associated virus (AAV)-based gene therapy, efficacy and toxicity screening have become essential for developing gene therapeutic drugs for retinal diseases. Retinal organoids from human pluripotent stem cells (hPSCs) offer a more accessible and reproducible human test platform for evaluating AAV-based gene therapy. In this study, hPSCs were differentiated into retinal organoids composed of various types of retinal cells. The transduction efficiencies of AAV2 and AAV8, which are widely used in clinical trials of inherited retinal diseases, were analyzed using retinal organoids. These results suggest that retinal organoids derived from hPSCs serve as suitable screening platforms owing to their diverse retinal cell types and similarity to the human retina. In summary, we propose an optimal stepwise protocol that includes the generation of retinal organoids and analysis of AAV transduction efficacy, providing a comprehensive approach for evaluating AAV-based gene therapy for retinal diseases.

中文翻译：

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人类多能干细胞衍生的视网膜类器官：研究腺相关病毒基因治疗功效的可行平台。

随着基于腺相关病毒（AAV）的基因治疗的最新进展，功效和毒性筛选对于开发视网膜疾病基因治疗药物至关重要。来自人类多能干细胞 (hPSC) 的视网膜类器官为评估基于 AAV 的基因治疗提供了一个更容易获得和可重复的人体测试平台。在这项研究中，hPSC 分化为由各种类型的视网膜细胞组成的视网膜类器官。使用视网膜类器官分析了广泛用于遗传性视网膜疾病临床试验的 AAV2 和 AAV8 的转导效率。这些结果表明，源自 hPSC 的视网膜类器官由于其视网膜细胞类型多样且与人类视网膜相似，可作为合适的筛选平台。总之，我们提出了一种最佳的逐步方案，包括视网膜类器官的生成和 AAV 转导功效的分析，为评估基于 AAV 的视网膜疾病基因治疗提供了综合方法。