Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases

被引：74
作者：
Keeling, Kim M. [1 ]
Bedwell, David M. [1 ]
机构：
[1] Univ Alabama Birmingham, Dept Microbiol, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA
来源：
WILEY INTERDISCIPLINARY REVIEWS-RNA | 2011年 / 2卷 / 06期
关键词：
MESSENGER-RNA DECAY; TRANSLATIONAL TERMINATION EFFICIENCY; PREMATURE STOP MUTATIONS; CYSTIC-FIBROSIS PATIENTS; ALPHA-L-IDURONIDASE; DYSTROPHIN EXPRESSION; CRYSTAL-STRUCTURE; READ-THROUGH; IN-VITRO; AMINOGLYCOSIDE;
D O I：
10.1002/wrna.95
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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. (c) 2011 John Wiley & Sons, Ltd. WIREs RNA 2011 2 837-852 DOI: 10.1002/wrna.95
引用
收藏
页码：837 / 852
页数：16
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