title: Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs).
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.
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-University of Mainz, Johannes-von-Mueller-Weg 6, 55099, Mainz, Germany. nagelwol@uni-mainz.de.|Focus Program Translational Neurosciences (FTN), Johannes Gutenberg-University of Mainz, 55122, Mainz, Germany. nagelwol@uni-mainz.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nagel-Wolfrum
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-University of Mainz, Johannes-von-Mueller-Weg 6, 55099, Mainz, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Möller
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-University of Mainz, Johannes-von-Mueller-Weg 6, 55099, Mainz, Germany.
authors.forename: Inessa
authors.initials: I
authors.lastname: Penner
authors.affiliation: Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Timor
authors.initials: T
authors.lastname: Baasov
authors.affiliation: Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg-University of Mainz, Johannes-von-Mueller-Weg 6, 55099, Mainz, Germany.|Focus Program Translational Neurosciences (FTN), Johannes Gutenberg-University of Mainz, 55122, Mainz, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
mesh_terms: D000818:Animals; D018389:Codon, Nonsense / Q000187:drug effects*; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005838:Genotype; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger