Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We?
Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We?
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DOI：
10.2147/tacg.s383453
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发表时间：
2023
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由于其体积小且安全，腺相关病毒（AAV）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 之外，还正在开发几种具有增强特性的工程变体，用于实验和治疗应用。尽管如此，仍然存在一些挑战阻碍 AAV 成功应用于更广泛的视网膜基因治疗。 AAV 颗粒的小尺寸确保了有效的组织转导，但也将包装容量限制在几千碱基。此外，AAV 穿越视网膜屏障的能力仍然是在可耐受剂量下外视网膜全视网膜转导的障碍。最后，尽管总体安全，但最近有报道称 AAV 在眼睛中产生免疫反应。因此，对 AAV 免疫反应的评估和预测已被认为是未来临床成功不可或缺的一部分。本综述重点关注 AAV 在视网膜疾病临床试验中的应用，并讨论了克服 AAV 免疫反应的变异体和新策略的发展。
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.