Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)

  • Authors:
    • John Karijolich
    • Yi-Tao Yu
  • View Affiliations

  • Published online on: June 17, 2014     https://doi.org/10.3892/ijmm.2014.1809
  • Pages: 355-362
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Abstract

An estimated one-third of genetic disorders are the result of mutations that generate premature termination codons (PTCs) within protein coding genes. These disorders are phenotypically diverse and consist of diseases that affect both young and old individuals. Various small molecules have been identified that are capable of modulating the efficiency of translation termination, including select antibiotics of the aminoglycoside family and multiple novel synthetic molecules, including PTC124. Several of these agents have proved their effectiveness at promoting nonsense suppression in preclinical animal models, as well as in clinical trials. In addition, it has recently been shown that box H/ACA RNA-guided peudouridylation, when directed to modify PTCs, can also promote nonsense suppression. In this review, we summarize our current understanding of eukaryotic translation termination and discuss various methods for promoting the read-through of disease-causing PTCs, as well as the current obstacles that stand in the way of using the discussed agents broadly in clinical practice.
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August-2014
Volume 34 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Karijolich J and Yu Y: Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). Int J Mol Med 34: 355-362, 2014.
APA
Karijolich, J., & Yu, Y. (2014). Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review). International Journal of Molecular Medicine, 34, 355-362. https://doi.org/10.3892/ijmm.2014.1809
MLA
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34.2 (2014): 355-362.
Chicago
Karijolich, J., Yu, Y."Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)". International Journal of Molecular Medicine 34, no. 2 (2014): 355-362. https://doi.org/10.3892/ijmm.2014.1809