Publication
G418 as a suppression therapy for beta-thalassemia disease
| dc.contributor.author | Dias, Patrícia | |
| dc.contributor.author | Gomes-Duarte, Andreia | |
| dc.contributor.author | Romão, Luísa | |
| dc.date.accessioned | 2018-03-02T16:49:07Z | |
| dc.date.embargo | 2025-12-31 | |
| dc.date.issued | 2017-11-16 | |
| dc.description.abstract | Premature translation-termination codons (PTCs or nonsense codons) can arise from mutations in germ or somatic cells. The introduction of a PTC into an mRNA can trigger nonsense-mediated decay (NMD), an important mRNA surveillance mechanism that typically recognizes and degrades mRNAs containing PTCs to prevent the synthesis of C-terminally truncated proteins potentially toxic for the cell. The physiological relevance of NMD is manifested by the fact that about one third of genetic disease-associated mutations generate PTCs, including -thalassemia. In recent years, a novel therapeutic approach entitled suppression therapy has been developed based on low molecular weight compounds to induce the translation machinery to recode a PTC into a sense codon, the so called “readthrough” (or suppression). Here, by using a model of constructs containing the 5’ part of the normal, or nonsense-mutated, human -globin gene fused to the firefly luciferase gene as a reporter, we intend to prove the principle that the suppression therapy can restore enough -globin protein to outweight the manifestations of -thalassemia. Our results from bioluminescence assays and Western blot analyses have shown that the aminoglycoside G418 is able to suppress a nonsense mutation at codon 15 or 39 of the human -globin mRNA, in cultured HEK293 cells. We are now interested in stablishing how NMD inhibition can increase the efficiency of suppression therapy. A depper study on the suppression therapy is crucial, as it offers a major approach to treat a wide range of inherited pathologies. | pt_PT |
| dc.description.sponsorship | This work is partially supported by Fundação para a Ciência e a Tecnologia (PTDC/BIM-MEC/3749/2014). | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/5141 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.subject | Premature Translation-termination Codons | pt_PT |
| dc.subject | mRNA Mechanism | pt_PT |
| dc.subject | Expressão Génica | pt_PT |
| dc.subject | Genómica Funcional e Estrutural | pt_PT |
| dc.subject | Beta-thalassemia Disease | |
| dc.title | G418 as a suppression therapy for beta-thalassemia disease | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Caparica, Portugal | pt_PT |
| oaire.citation.title | 21ª Reunião Anual da Sociedade Portuguesa de Genética Humana, 16-18 novembro 2017 | pt_PT |
| rcaap.embargofct | Os resultados ainda não foram publicados | pt_PT |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |