| dc.contributor.advisor | Thoms, Sven Prof. Dr. | |
| dc.contributor.author | Schilff, Mirco | |
| dc.date.accessioned | 2025-05-19T14:37:32Z | |
| dc.date.available | 2025-07-16T00:50:10Z | |
| dc.date.issued | 2025-05-19 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/16001 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-11267 | |
| dc.description.sponsorship | Promotionskolleg für Medizinstudierende der Universitätsmedizin Göttingen, Else Kröner-Fresenius-Kolleg, Jacob-Henle-Programm | de |
| dc.description.sponsorship | Promotionskolleg für Medizinstudierende der Universitätsmedizin Göttingen, Else Kröner-Fresenius-Kolleg, Jacob-Henle-Programm | de |
| dc.format.extent | 71 | de |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Untersuchung von Translationalem Readthrough bei Peroxisomalen Biogenesestörungen im Zellmodell | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Thoms, Sven Prof. Dr. | |
| dc.date.examination | 2025-06-18 | de |
| dc.description.abstracteng | Premature termination codon (PTC) mutations account for approximately 10% of pathogenic
variants in monogenic diseases. Stimulation of translational readthrough, also known as stop codon
suppression, using translational readthrough-inducing drugs (TRIDs) may serve as a possible therapeutic
strategy for the treatment of genetic PTC diseases. One important parameter governing
readthrough is the stop codon context (SCC)—the stop codon itself and the nucleotides in the
vicinity of the stop codon on the mRNA. However, the quantitative influence of the SCC on treatment
outcome and on appropriate drug concentrations are largely unknown. Here, we analyze the
readthrough-stimulatory effect of various readthrough-inducing drugs on the SCCs of five common
premature termination codon mutations of PEX5 in a sensitive dual reporter system. Mutations in
PEX5, encoding the peroxisomal targeting signal 1 receptor, can cause peroxisomal biogenesis disorders
of the Zellweger spectrum. We show that the stop context has a strong influence on the levels
of readthrough stimulation and impacts the choice of the most effective drug and its concentration.
These results highlight potential advantages and the personalized medicine nature of an SCC-based
strategy in the therapy of rare diseases. | de |
| dc.contributor.coReferee | Kehlenbach, Ralph Prof. Dr. | |
| dc.subject.eng | translational readthrough; rare disease; peroxisome; peroxisome biogenesis disorder; PEX5; personalized medicine; readthrough therapy; aminoglycoside | de |
| dc.subject.eng | translational readthrough; rare disease; peroxisome; peroxisome biogenesis disorder; PEX5; personalized medicine; readthrough therapy; aminoglycoside | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-16001-3 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Pädiatrie / Neonatologie / Kinderchirurgie - Allgemein- und Gesamtdarstellungen (PPN619876093) | de |
| dc.subject.gokfull | Pädiatrie / Neonatologie / Kinderchirurgie - Allgemein- und Gesamtdarstellungen (PPN619876093) | de |
| dc.description.embargoed | 2025-07-16 | de |
| dc.identifier.ppn | 1926164075 | |
| dc.notes.confirmationsent | Confirmation sent 2025-05-19T14:45:01 | de |