Généthon, CNRS/UEVE UMR8587 LAMBE, 1, rue de l'Internationale, 91000 Evry, France.
Trends Mol Med. 2009 Dec;15(12):580-91. doi: 10.1016/j.molmed.2009.10.005. Epub 2009 Nov 10.
Although most molecular therapy strategies for genetic diseases are based on gene replacement, interesting alternative approaches target RNA. These strategies rely on the modification of the mutated gene's expression in vivo by modulating pre-mRNA splicing, mRNA stability or mRNA translation. Here, we review recent progress using these RNA-based approaches in the field of muscle and muscle-related genetic diseases. Different molecular tools, including modified antisense oligonucleotides, pre-mRNA trans-splicing molecules, ribozymes or chemical compounds have been used successfully on patient cells or animal models of disease. These diverse strategies show tremendous therapeutic potential and several clinical trials have been initiated with Duchenne muscular dystrophy patients with promising results.
尽管大多数遗传性疾病的分子治疗策略都基于基因替换，但有趣的替代方法靶向 RNA。这些策略依赖于通过调节前体 mRNA 剪接、mRNA 稳定性或 mRNA 翻译来体内修饰突变基因的表达。在这里，我们综述了在肌肉和肌肉相关遗传性疾病领域中使用这些基于 RNA 的方法的最新进展。不同的分子工具，包括修饰后的反义寡核苷酸、前体 mRNA 转剪接分子、核酶或化学化合物，已成功用于患者细胞或疾病动物模型中。这些不同的策略显示出巨大的治疗潜力，并且已经启动了针对杜氏肌营养不良症患者的几项临床试验，结果令人鼓舞。
