促通读药物的作用机制与临床应用-遗传.PDFVIP

Hereditas (Beijing) 2016 年 7 月, 38(7): 623―633 综 述 促通读药物的作用机制与临床应用 付洋，舒在悦，顾鸣敏 200025 摘要: 据统计，全球有近1/10 的遗传病由无义突变(Nonsense mutation)所致。无义突变通常导致翻译提前终止，生 成截短的、无功能的蛋白质。近年来，促通读药物在无义突变所致遗传病的治疗方面取得了明显进展。然而，由于 翻译终止的机制仍不甚明了，因此促通读药物的机制研究和临床应用面临着新的挑战。本文主要探讨了促通读药物 治疗无义突变所致遗传病的作用机制，以及促通读药物在临床应用方面的研究进展、存在的问题及应对策略。 关键词: 遗传病；无义突变；促通读药物；作用机制；临床应用 The functional mechanisms and clinical application of read-through drugs Yang Fu, Zaiyue Shu, Mingmin Gu School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China Abstract: According to previous reports, nearly one in 10 genetic diseases are caused by nonsense mutations around the world. Nonsense mutations lead to premature transcription terminations in cells, which in turn generate non-functional, truncated proteins. In recent years, read-through drugs are playing increasing prominent roles in the researches related to genetic diseases caused by nonsense mutations. However, due to the fact that the mechanisms lying behind translation ter- mination still remain to be elucidated, the mechanistic research and clinical application of read-through drugs are facing new challenges. This review mainly discusses about the pathogenesis of genetic diseases caused by nonsense mutations, and then introduces the current clinical application of read-through drugs. Finally, we display some problems that remain to be solved and propose some possible coping strategies. Keywords: genetic disease; nonsense mutation; read-through drug; functional mechanism; clinical application (Duchenne mus- cular dystrophy, DMD)(Cystic fibrosis,