Li W Y, Sui R F
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhonghua Yan Ke Za Zhi. 2023 Dec 11;59(12):1058-1064. doi: 10.3760/cma.j.cn112142-20231024-00169.
Biallelic pathogenic variants in the USH2A gene result in Usher syndrome type Ⅱ and non-syndromic retinitis pigmentosa, both of which entail the progressive loss of photoreceptors leading to blindness. The cDNA of the USH2A gene is extensive, consisting of 15 606 base pairs, rendering it impractical for delivery via adeno-associated virus vectors for gene replacement therapy. Notably, exon 13 has emerged as a focal point for therapeutic intervention, given its predilection for harboring the most pathogenic variants within USH2A. Recent intervention studies targeting USH2A exon 13 through the utilization of antisense oligonucleotides, genome editing, and RNA editing approaches have exhibited promising therapeutic potential. This paper provides a comprehensive overview of the molecular mechanisms, outcome data, and the challenges associated with the application of these interventions in this domain.
USH2A基因的双等位基因致病变异会导致Ⅱ型Usher综合征和非综合征性视网膜色素变性，这两种疾病都会导致光感受器逐渐丧失，最终导致失明。USH2A基因的cDNA很长，由15606个碱基对组成，因此通过腺相关病毒载体进行基因替代治疗来递送该基因是不切实际的。值得注意的是，鉴于外显子13倾向于携带USH2A基因中最具致病性的变异，它已成为治疗干预的重点。最近通过使用反义寡核苷酸、基因组编辑和RNA编辑方法针对USH2A外显子13进行的干预研究显示出了有前景的治疗潜力。本文全面概述了这些干预措施在该领域应用的分子机制、结果数据以及相关挑战。
