Ail Divya, Malki Hugo, Zin Emilia A, Dalkara Deniz
Sorbonne Université, INSERM, CNRS, Department of Therapeutics, Institut de la Vision, Paris, 75012, France.
Appl Clin Genet. 2023 May 30;16:111-130. doi: 10.2147/TACG.S383453. eCollection 2023.
Owing to their small size and safety profiles, adeno-associated viruses (AAVs) have become the vector of choice for gene therapy applications in the retina. In addition to the naturally occurring AAVs, several engineered variants with enhanced properties are being developed for experimental and therapeutic applications. Nonetheless, there are still some challenges impeding successful application of AAVs for a broader range of retinal gene therapies. The small size of AAV particles ensures efficient tissue transduction but also limits the packaging capacity to a few kilobases. Further, AAV's ability to cross retinal barriers is still an obstacle to pan-retinal transduction of the outer retina with tolerable doses. Lastly, despite overall safety, there have been recent reports of immune responses to AAVs in the eye. Hence, evaluation and prediction of immune responses to AAVs has come to be considered an integral part of future clinical success. This review focuses on the use of AAV in clinical trials for retinal diseases, and discusses developments of variants and novel strategies to overcome immune responses to AAVs.
由于腺相关病毒（AAV）体积小且安全性良好，它们已成为视网膜基因治疗应用的首选载体。除了天然存在的AAV外，几种具有增强特性的工程变体也正在被开发用于实验和治疗应用。尽管如此，仍然存在一些挑战阻碍了AAV在更广泛的视网膜基因治疗中的成功应用。AAV颗粒的小尺寸确保了有效的组织转导，但也将包装能力限制在几千碱基对。此外，AAV穿越视网膜屏障的能力仍然是在外视网膜以可耐受剂量进行全视网膜转导的障碍。最后，尽管总体安全，但最近有报道称眼睛对AAV会产生免疫反应。因此，对AAV免疫反应的评估和预测已被视为未来临床成功的一个不可或缺的部分。本综述重点关注AAV在视网膜疾病临床试验中的应用，并讨论变体的开发以及克服对AAV免疫反应的新策略。
