Fu Yang, Shu Zai-yue, Gu Ming-min
School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Yi Chuan. 2016 Jul 20;38(7):623-633. doi: 10.16288/j.yczz.15-519.
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 termination 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.
根据以往报道,全球近十分之一的遗传疾病由无义突变引起。无义突变导致细胞内转录提前终止,进而产生无功能的截短蛋白。近年来,通读药物在由无义突变引起的遗传疾病相关研究中发挥着越来越重要的作用。然而,由于翻译终止背后的机制仍有待阐明,通读药物的机制研究和临床应用面临新的挑战。本综述主要探讨无义突变引起的遗传疾病的发病机制,然后介绍通读药物目前的临床应用情况。最后,我们展示了一些有待解决的问题并提出了一些可能的应对策略。