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Suppression therapy as novel approach for genetic diseases and cancer

2017-05-08Conference object Restricted access
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dc.contributor.authorGomes-Duarte, Andreia
dc.contributor.authorDias, Parícia
dc.contributor.authorRomão, Luísa
dc.date.accessioned2018-03-05T11:14:40Z
dc.date.embargo2025-12-31
dc.date.issued2017-05-08
dc.description.abstractPremature 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 importance of NMD is manifested by the fact that about one third of genetic disease-associated mutations generate PTCs, including beta-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”. Here, by using a model of constructs containing the firefly luciferase gene as a reporter gene for beta-globin transcripts that result from PTCs, we intend to prove the principle that the suppression therapy can restore enough beta-globin protein to outweight the disease manifestations of beta-thalassemia. Our preliminary results show that both the aminoglycoside G418 and non-aminoglycoside PTC124 do not seem to be able to suppress the nonsense mutation at codon 26 or 39 of the human beta-globin mRNA in cultured HeLa cells, as reflected on the firefly luciferase activity and protein levels assessed by bioluminescence assays and Western blot, respectively. Regarding future directions, a deeper study on the use of G418 and PTC124 as efficient suppression agents for the treatment of PTC-associated diseases will be performed as it offers a major potential to treat a wide range of inherited pathologies.pt_PT
dc.description.sponsorshipThis work is partially supported by Fundação para a Ciência e aTecnologia (PTDC/BIM-MEC/3749/2014).pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/5153
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectSuppression Therapypt_PT
dc.subjectGenetic Diseasespt_PT
dc.subjectCancerpt_PT
dc.subjectPremature Translation-termination Codonspt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectExpressão Génicapt_PT
dc.titleSuppression therapy as novel approach for genetic diseases and cancerpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.title2º Dia do Jovem Investigador do Instituto Nacional de Saúde Doutor Ricardo Jorge, 8 maio 2017pt_PT
rcaap.embargofctOs resultados ainda não foram publicadospt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT

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