Introducing sense into nonsense in treatments of human genetic diseases
Introducing sense into nonsense in treatments of human genetic diseases
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DOI：
10.1016/j.tig.2008.08.010
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发表时间：
2008-11-01
影响因子：
11.4
通讯作者：
Kerem, Batsheva
中科院分区：
文献类型：
--
作者：
Linde, Liat;Kerem, Batsheva
大约三分之一的导致遗传疾病的等位基因携带提前终止密码子（PTC），这导致产生截短的蛋白质。在过去的十年中，人们对旨在通读框内PTC以合成全长蛋白质的治疗方法产生了相当大的兴趣。然而，在许多疾病中通读PTC的尝试导致了可变的效果。在这里，我们专注于囊性纤维化和Duchenne肌营养不良症的治疗方法的努力，并讨论成功通读的因素，以及无义介导的mRNA衰变（NMD）途径如何调节这种反应。有必要更深入地了解PTCs通读的可变反应的分子基础，以便开发适当的疗法来治疗由PTCs引起的许多人类遗传疾病。
Approximately one-third of alleles causing genetic diseases carry premature termination codons (PTCs), which lead to the production of truncated proteins. The past decade has seen considerable interest in therapeutic approaches aimed at readthrough of in-frame PTCs to enable synthesis of full-length proteins. However, attempts to readthrough PTCs in many diseases resulted in variable effects. Here, we focus on the efforts of such therapeutic approaches in cystic fibrosis and Duchenne muscular dystrophy and discuss the factors contributing to successful readthrough and how the nonsense-mediated mRNA decay (NMD) pathway regulates this response. A deeper understanding of the molecular basis for variable response to readthrough of PTCs is necessary so that appropriate therapies can be developed to treat many human genetic diseases caused by PTCs.