抑制无义突变作为治疗遗传疾病的一种方法。
Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases.
机构信息
Department of Microbiology, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
出版信息
Wiley Interdiscip Rev RNA. 2011 Nov-Dec;2(6):837-52. doi: 10.1002/wrna.95. Epub 2011 Jul 6.
Abstract
Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy.
摘要
抑制疗法是一种针对无义突变引起的遗传疾病的治疗策略。这种治疗方法利用药理学制剂抑制框架内的过早终止密码子（PTC）的翻译终止，以恢复全长功能性多肽的翻译。讨论了各种化合物在哺乳动物细胞中抑制 PTC 的效率，以及该疗法的当前局限性。我们还详细介绍了提高抑制效率的方法，包括增强现有抑制药物效果的方法，以及设计或发现新的、更有效的抑制剂。最后，我们讨论了无义介导的 mRNA 降解（NMD）在限制抑制疗法有效性方面的作用，并描述了可能允许调节 NMD 效率以增强抑制疗法的策略。
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