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BioDrugs
Published in: BioDrugs 2/2016

01-04-2016 | Leading Article

Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs)

Authors: Kerstin Nagel-Wolfrum, Fabian Möller, Inessa Penner, Timor Baasov, Uwe Wolfrum

Published in: BioDrugs | Issue 2/2016

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Abstract

In recent years, remarkable advances in the ability to diagnose genetic disorders have been made. The identification of disease-causing genes allows the development of gene-specific therapies with the ultimate goal to develop personalized medicines for each patient according to their own specific genetic defect. In-depth genotyping of many different genes has revealed that ~12 % of inherited genetic disorders are caused by in-frame nonsense mutations. Nonsense (non-coding) mutations are caused by point mutations, which generate premature termination codons (PTCs) that cause premature translational termination of the mRNA, and subsequently inhibit normal full-length protein expression. Recently, a gene-based therapeutic approach for genetic diseases caused by nonsense mutations has emerged, namely the so-called translational read-through (TR) therapy. Read-through therapy is based on the discovery that small molecules, known as TR-inducing drugs (TRIDs), allow the translation machinery to suppress a nonsense codon, elongate the nascent peptide chain, and consequently result in the synthesis of full-length protein. Several TRIDs are currently under investigation and research has been performed on several genetic disorders caused by nonsense mutations over the years. These findings have raised hope for the usage of TR therapy as a gene-based pharmacogenetic therapy for nonsense mutations in various genes responsible for a variety of genetic diseases.
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Metadata
Title
Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs)
Authors
Kerstin Nagel-Wolfrum
Fabian Möller
Inessa Penner
Timor Baasov
Uwe Wolfrum
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
BioDrugs / Issue 2/2016
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI
https://doi.org/10.1007/s40259-016-0157-6

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