Therapeutics based on stop codon readthrough.
Therapeutics based on stop codon readthrough.
复制标题
DOI：
10.1146/annurev-genom-091212-153527
复制
发表时间：
2014
影响因子：
8.7
通讯作者：
Bedwell DM
中科院分区：
文献类型：
--
作者：
Keeling KM;Xue X;Gunn G;Bedwell DM
无义抑制疗法包括旨在抑制框内提前终止密码子（PTC，也称为无义突变）处的翻译终止以恢复缺陷蛋白质功能的方法。在这篇综述中，我们研究了PTC抑制作为无义突变引起的遗传性疾病的治疗方法的现状。我们讨论了目前已知的PTC抑制机制以及正在开发的抑制PTC的治疗方法。所考虑的方法包括通读药物、抑制性tRNA、PTC假尿苷酸化和抑制无义介导的mRNA衰变。我们还讨论了目前限制无意义抑制治疗的临床应用的障碍，并建议如何克服这些困难。最后，我们考虑PTC抑制如何在无义突变引起的遗传性疾病的临床治疗中发挥作用。
Nonsense suppression therapy encompasses approaches aimed at suppressing translation termination at in-frame premature termination codons (PTCs, also known as nonsense mutations) to restore deficient protein function. In this review, we examine the current status of PTC suppression as a therapy for genetic diseases caused by nonsense mutations. We discuss what is currently known about the mechanism of PTC suppression as well as therapeutic approaches under development to suppress PTCs. The approaches considered include readthrough drugs, suppressor tRNAs, PTC pseudouridylation, and inhibition of nonsense-mediated mRNA decay. We also discuss the barriers that currently limit the clinical application of nonsense suppression therapy and suggest how some of these difficulties may be overcome. Finally, we consider how PTC suppression may play a role in the clinical treatment of genetic diseases caused by nonsense mutations.