A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Tobias Goldmann
- Nora Overlack
- Fabian Möller
- Valery Belakhov
- Michiel Van Wyk
- Timor Baasov
- Uwe Wolfrum
- Kerstin Nagel-Wolfrum
- Sammlungen
- metadata
- ISSN
- 1757-4684
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- EMBO molecular medicine
- Schlüsselwörter
- 570 Biowissenschaften
- 570 Life sciences
- Sprache
- eng
- Paginierung
- Seiten: 1186 - 1199
- Datum der Veröffentlichung
- 2012
- Herausgeber
- Wiley-VCH
- Herausgeber URL
- http://dx.doi.org/10.1002/emmm.201201438
- Datum der Datenerfassung
- 2020
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Zugang
- Public
- Titel
- A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
- Ausgabe der Zeitschrift
- 4
Data source: METADATA.UB
- Other metadata sources:
-
- Autoren
- Tobias Goldmann
- Nora Overlack
- Fabian Moeller
- Valery Belakhov
- Michiel van Wyk
- Timor Baasov
- Uwe Wolfrum
- Kerstin Nagel-Wolfrum
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000310599100005&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/emmm.201201438
- eISSN
- 1757-4684
- Externe Identifier
- Clarivate Analytics Document Solution ID: 030VV
- PubMed Identifier: 23027640
- ISSN
- 1757-4676
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- EMBO MOLECULAR MEDICINE
- Schlüsselwörter
- drug therapy
- pharmacogenetics
- retinitis pigmentosa
- sensoneuronal degeneration
- Usher syndrome
- Paginierung
- 1186 - 1199
- Datum der Veröffentlichung
- 2012
- Status
- Published
- Titel
- A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an <i>USH1C</i> nonsense mutation
- Sub types
- Article
- Ausgabe der Zeitschrift
- 4
Data source: Web of Science (Lite)
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Translational read‐through‐inducing drugs (TRIDs) promote read‐through of nonsense mutations, placing them in the spotlight of current gene‐based therapeutic research. Here, we compare for the first time the relative efficacies of new‐generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read‐through efficacy of a nonsense mutation in the <jats:italic>USH1C</jats:italic> gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf‐blindness. We quantify read‐through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read‐through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read‐through <jats:italic>versus</jats:italic> toxicity evidently superior for NB54 and PTC124. In addition, <jats:italic>in vivo</jats:italic> administration of NB54 and PTC124 induced recovery of the full‐length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read‐through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation‐based retinal disorders.</jats:p>
- Autoren
- Tobias Goldmann
- Nora Overlack
- Fabian Möller
- Valery Belakhov
- Michiel van Wyk
- Timor Baasov
- Uwe Wolfrum
- Kerstin Nagel‐Wolfrum
- DOI
- 10.1002/emmm.201201438
- eISSN
- 1757-4684
- ISSN
- 1757-4676
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- EMBO Molecular Medicine
- Sprache
- en
- Online publication date
- 2012
- Paginierung
- 1186 - 1199
- Datum der Veröffentlichung
- 2012
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1002/emmm.201201438
- Datum der Datenerfassung
- 2023
- Titel
- A comparative evaluation of NB30, NB54 and PTC124 in translational read‐through efficacy for treatment of an <i>USH1C</i> nonsense mutation
- Ausgabe der Zeitschrift
- 4
Data source: Crossref
- Abstract
- Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read-through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read-through versus toxicity evidently superior for NB54 and PTC124. In addition, in vivo administration of NB54 and PTC124 induced recovery of the full-length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read-through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation-based retinal disorders.
- Addresses
- Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Germany.
- Autoren
- Tobias Goldmann
- Nora Overlack
- Fabian Möller
- Valery Belakhov
- Michiel van Wyk
- Timor Baasov
- Uwe Wolfrum
- Kerstin Nagel-Wolfrum
- DOI
- 10.1002/emmm.201201438
- eISSN
- 1757-4684
- Externe Identifier
- PubMed Identifier: 23027640
- PubMed Central ID: PMC3494875
- Open access
- true
- ISSN
- 1757-4676
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- EMBO molecular medicine
- Schlüsselwörter
- Retina
- Cell Line
- Animals
- Mice, Inbred C57BL
- Humans
- Mice
- Retinal Diseases
- Oxadiazoles
- Aminoglycosides
- Adaptor Proteins, Signal Transducing
- Cell Cycle Proteins
- Cytoskeletal Proteins
- Codon, Nonsense
- Peptide Chain Elongation, Translational
- Female
- Male
- In Vitro Techniques
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2012
- Open access status
- Open Access
- Paginierung
- 1186 - 1199
- Datum der Veröffentlichung
- 2012
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2012
- Titel
- A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation.
- Sub types
- Comparative Study
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 4
Files
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/emmm.201201438 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23027640/pdf/?tool=EBI https://europepmc.org/articles/PMC3494875?pdf=render
Data source: Europe PubMed Central
- Abstract
- Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read-through efficacy of the TRIDs in retinal cultures; however, we show an excellent biocompatibility in retinal cultures with read-through versus toxicity evidently superior for NB54 and PTC124. In addition, in vivo administration of NB54 and PTC124 induced recovery of the full-length harmonin a1 with the same efficacy. The high biocompatibilities combined with the sustained read-through efficacies of these drugs emphasize the potential of NB54 and PTC124 in treating nonsense mutation-based retinal disorders.
- Date of acceptance
- 2012
- Autoren
- Tobias Goldmann
- Nora Overlack
- Fabian Möller
- Valery Belakhov
- Michiel van Wyk
- Timor Baasov
- Uwe Wolfrum
- Kerstin Nagel-Wolfrum
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/23027640
- DOI
- 10.1002/emmm.201201438
- eISSN
- 1757-4684
- Externe Identifier
- PubMed Central ID: PMC3494875
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- EMBO Mol Med
- Schlüsselwörter
- Adaptor Proteins, Signal Transducing
- Aminoglycosides
- Animals
- Cell Cycle Proteins
- Cell Line
- Codon, Nonsense
- Cytoskeletal Proteins
- Female
- Humans
- In Vitro Techniques
- Male
- Mice
- Mice, Inbred C57BL
- Oxadiazoles
- Peptide Chain Elongation, Translational
- Retina
- Retinal Diseases
- Sprache
- eng
- Country
- Germany
- Paginierung
- 1186 - 1199
- Datum der Veröffentlichung
- 2012
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2013
- Titel
- A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation.
- Sub types
- Comparative Study
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 4
Data source: PubMed
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