Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases
- 6 July 2011
- Vol. 2 (6), 837-852
- https://doi.org/10.1002/wrna.95
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. WIREs RNA 2011 2 837–852 DOI: 10.1002/wrna.95 Correction added on July 13 2011, after first online publication. Figure 5 was incorrect and has been replaced. This article is categorized under: Translation > Translation Mechanisms RNA in Disease and Development > RNA in DiseaseKeywords
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