Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient’s genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism.

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反义寡核苷酸治疗遗传性儿童肺部疾病的潜力

反义寡核苷酸是一种新兴的治疗选择，用于治疗已知遗传起源的疾病。在个性化药物时代，有时可以设计反义寡核苷酸来靶向和绕过或克服患者的基因突变，特别是那些损害正常前 mRNA 加工的病变。反义寡核苷酸可以通过化学和反义寡聚体设计所确定的多种机制来改变基因表达。通过靶向前体 mRNA，反义寡核苷酸可以改变剪接并诱导特定的剪接形式或破坏阅读框，靶向 RNA 转录物以通过 RNaseH 激活降解，阻断蛋白质翻译的核糖体起始或破坏 miRNA 功能。最近美国食品和药物管理局加速批准 eteplirsen（更名为 Exondys 51™）用于治疗杜氏肌营养不良症和 nusinersen 用于治疗脊髓性肌萎缩症，预示着剪接转换反义寡核苷酸进入一个令人兴奋的新时代应用于治疗遗传性疾病。本综述考虑了反义寡核苷酸治疗儿童遗传性肺病的潜力，重点是囊性纤维化和表面活性蛋白代谢紊乱。