Antisense oligonucleotides (ASOs) can modulate pre-mRNA splicing. This offers therapeutic opportunities for numerous genetic diseases, often in a mutation-specific and sometimes even individual-specific manner. Developing therapeutic ASOs for as few as even a single patient has been shown feasible with the development of Milasen for an individual with Batten disease. Efforts to develop individualized ASOs for patients with different genetic diseases are ongoing globally. The N = 1 Collaborative (N1C) is an umbrella organization dedicated to supporting the nascent field of individualized medicine. N1C recently organized a workshop to discuss and advance standards for the rigorous design and testing of splice-switching ASOs. In this study, we present guidelines resulting from that meeting and the key recommendations: (1) dissemination of standardized experimental designs, (2) use of standardized reference ASOs, and (3) a commitment to data sharing and exchange.

中文翻译：

---

N-of-1 外显子跳跃反义寡核苷酸设计和体外临床前功效测试的共识指南

反义寡核苷酸 (ASO) 可以调节 pre-mRNA 剪接。这为许多遗传疾病提供了治疗机会，通常以突变特异性，有时甚至是个体特异性的方式。为患有 Batten 病的个体开发 Milasen 已证明，为少至单个患者开发治疗性 ASO 是可行的。全球都在努力为患有不同遗传病的患者开发个体化 ASO。N = 1 Collaborative (N1C) 是一个伞式组织，致力于支持新兴的个体化医学领域。N1C 最近组织了一个研讨会，讨论和推进熔接交换 ASO 的严格设计和测试标准。在本研究中，我们提出了该会议的指导方针和主要建议：