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首页> 外文期刊>Journal of Personalized Medicine >Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges
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Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges

机译：杜兴氏肌肉营养不良热点中的多个外显子跳过：前景和挑战。

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摘要

Duchenne muscular dystrophy (DMD), a fatal X-linked recessive disorder, is caused mostly by frame-disrupting, out-of-frame deletions in the dystrophin ( DMD ) gene. Antisense oligonucleotide-mediated exon skipping is a promising therapy for DMD. Exon skipping aims to convert out-of-frame mRNA to in-frame mRNA and induce the production of internally-deleted dystrophin as seen in the less severe Becker muscular dystrophy. Currently, multiple exon skipping has gained special interest as a new therapeutic modality for this approach. Previous retrospective database studies represented a potential therapeutic application of multiple exon skipping. Since then, public DMD databases have become more useful with an increase in patient registration and advances in molecular diagnosis. Here, we provide an update on DMD genotype-phenotype associations using a global DMD database and further provide the rationale for multiple exon skipping development, particularly for exons 45–55 skipping and an emerging therapeutic concept, exons 3–9 skipping. Importantly, this review highlights the potential of multiple exon skipping for enabling the production of functionally-corrected dystrophin and for treating symptomatic patients not only with out-of-frame deletions but also those with in-frame deletions. We will also discuss prospects and challenges in multiple exon skipping therapy, referring to recent progress in antisense chemistry and design, as well as disease models.
机译：Duchenne肌营养不良症（DMD）是一种致命的X连锁隐性疾病，主要是由肌营养不良蛋白（DMD）基因中破坏帧的，构架外缺失引起的。反义寡核苷酸介导的外显子跳跃是一种有前途的DMD治疗方法。跳过外显子的目的是将框架外mRNA转换为框架内mRNA，并诱导内部缺失的肌营养不良蛋白的产生，这在较不严重的贝克尔肌营养不良症中可见。当前，多次外显子跳跃作为这种方法的一种新的治疗方法已引起了特别的兴趣。以前的回顾性数据库研究代表了多种外显子跳跃的潜在治疗应用。从那时起，随着患者注册的增加和分子诊断的进步，公共DMD数据库变得越来越有用。在这里，我们使用全球DMD数据库提供了DMD基因型-表型关联的更新，并进一步提供了多个外显子跳跃发展的理论基础，特别是对于45-55号外显子跳跃和新兴的治疗概念，即3-9号外显子跳跃。重要的是，这篇综述强调了跳过多个外显子的潜力，这使得能够产生功能校正的肌营养不良蛋白，并且不仅可以治疗具有框外缺失的患者，还可以治疗具有框内缺失的症状患者。我们还将参考反义化学和设计以及疾病模型的最新进展，讨论多种外显子跳过疗法的前景和挑战。

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