Genetic medicine is offering hope as new therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of Leber Congenital Amaurosis (LCA), an inherited blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval. Numerous gene therapy clinical trials are ongoing for other eye diseases, and novel delivery systems, discovery of new drug targets and emerging technologies are currently driving the field forward. Targeting RNA, in particular, is an attractive therapeutic strategy for genetic disease that may have safety advantages over alternative approaches by avoiding permanent changes in the genome. In this regard, antisense oligonucleotides (ASO) and RNA interference (RNAi) are the currently popular strategies for developing RNA-targeted therapeutics. Enthusiasm has been further fuelled by the emergence of clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems that allow targeted manipulation of nucleic acids. RNA-targeting CRISPR-Cas systems now provide a novel way to develop RNA-targeted therapeutics and may provide superior efficiency and specificity to existing technologies. In addition, RNA base editing technologies using CRISPR-Cas and other modalities also enable precise alteration of single nucleotides. In this review, we showcase advances made by RNA-targeting systems for ocular disease, discuss applications of ASO and RNAi technologies, highlight emerging CRISPR-Cas systems and consider the implications of RNA-targeting therapeutics in the development of future drugs to treat eye disease.

随着针对许多以前无法治愈的疾病的新疗法不断涌现，遗传医学带来了希望。眼睛处于这些进步的最前沿，例如美国食品和药物管理局 (US FDA) 于 2017 年批准 Luxturna® 用于治疗一种形式的 Leber 先天性黑蒙 (LCA)，这是一种遗传性失明。Luxturna® 也是第一个体内人类基因疗法获得美国 FDA 批准。针对其他眼病的大量基因治疗临床试验正在进行中，新型递送系统、新药物靶标的发现和新兴技术目前正在推动该领域向前发展。特别是靶向 RNA 是一种有吸引力的遗传疾病治疗策略，通过避免基因组的永久性变化，它可能比替代方法具有安全优势。在这方面，反义寡核苷酸 (ASO) 和 RNA 干扰 (RNAi) 是目前流行的开发 RNA 靶向疗法的策略。成簇规律散布的短回文重复序列 (CRISPR)-CRISPR 相关 (Cas) 系统的出现进一步激发了人们的热情，这些系统允许对核酸进行靶向操作。靶向 RNA 的 CRISPR-Cas 系统现在提供了一种开发靶向 RNA 疗法的新方法，并且可以提供比现有技术更高的效率和特异性。此外，使用 CRISPR-Cas 和其他模式的 RNA 碱基编辑技术也可以实现单核苷酸的精确改变。在这篇综述中，我们展示了 RNA 靶向系统在治疗眼部疾病方面取得的进展，讨论了 ASO 和 RNAi 技术的应用，重点介绍了新兴的 CRISPR-Cas 系统，并考虑了 RNA 靶向疗法在未来治疗眼病药物开发中的意义.