Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
Adv Exp Med Biol. 2019;1185:71-77. doi: 10.1007/978-3-030-27378-1_12.
Inherited retinal dystrophies (IRDs) are genetic diseases affecting 1 in every 3000 individuals worldwide. Nowadays, more than 250 genes have been associated with different forms of IRD. In the last decade, it has been shown that gene therapy is a promising approach to correct the genetic defects underlying IRD. In fact, voretigene neparvovec-rzyl (Luxturna™), the first commercialized gene therapy drug to treat RPE65-associated Leber congenital amaurosis, has opened new venues. However, IRDs are highly heterogeneous at genetic level making the design of novel strategies complicated. Unfortunately, the size of several frequently mutated genes is not suitable for the approved conventional therapeutic viral vectors; therefore, there is an urgent need for the development of alternatives, such as those targeting the pre-mRNA. In this mini-review, the potential of RNA-based strategies for IRDs is discussed.
遗传性视网膜病变（IRDs）是一种遗传疾病，影响全球每 3000 人中的 1 人。如今，已有超过 250 个基因与不同形式的 IRD 相关。在过去的十年中，已经表明基因治疗是纠正 IRD 遗传缺陷的一种很有前途的方法。事实上，第一种商业化的基因治疗药物 voretigene neparvovec-rzyl（Luxturna™）用于治疗 RPE65 相关的莱伯先天性黑矇症，为该病的治疗开辟了新途径。然而，IRDs 在遗传水平上具有高度异质性，使得新型策略的设计变得复杂。不幸的是，几个经常发生突变的基因的大小不适合已批准的常规治疗性病毒载体；因此，迫切需要开发替代方法，如针对前体 mRNA 的方法。在这篇综述中，讨论了基于 RNA 的策略在 IRDs 治疗中的潜力。
