Antisense oligonucleotides (ASOs) are short oligonucleotides that can modify gene expression and mRNA splicing in the nervous system. The FDA has approved ASOs for treatment of ten genetic disorders, with many applications currently in the pipeline. We describe the molecular mechanisms of ASO treatment for four neurodevelopmental and neuromuscular disorders. The ASO nusinersen is a general treatment for mutations of SMN1 in spinal muscular atrophy that corrects the splicing defect in the SMN2 gene. Milasen is a patient-specific ASO that rescues splicing of CNL7 in Batten’s disease. STK-001 is an ASO that increases expression of the sodium channel gene SCN1A by exclusion of a poison exon. An ASO that reduces the abundance of the SCN8A mRNA is therapeutic in mouse models of developmental and epileptic encephalopathy. These examples demonstrate the variety of mechanisms and range of applications of ASOs for treatment of neurodevelopmental disorders.
Dev Neurosci

中文翻译：

---

神经发育障碍的反义寡核苷酸治疗

反义寡核苷酸 (ASO) 是短寡核苷酸，可以修饰神经系统中的基因表达和 mRNA 剪接。FDA 已批准 ASO 用于治疗十种遗传性疾病，目前有许多应用正在酝酿之中。我们描述了 ASO 治疗四种神经发育和神经肌肉疾病的分子机制。ASO nusinersen 是治疗脊髓性肌萎缩症SMN1突变的通用疗法，可纠正SMN2基因的剪接缺陷。Milasen 是一种患者特异性 ASO，可挽救巴顿病中CNL7的剪接。STK-001 是一种 ASO，通过排除毒物外显子来增加钠通道基因SCN1A的表达。减少SCN8A mRNA丰度的 ASO对发育性脑病和癫痫性脑病小鼠模型具有治疗作用。这些例子证明了 ASO 治疗神经发育障碍的多种机制和应用范围。
开发神经科学