Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy

Detalhes bibliográficos
Autor(a) principal: Matos, Liliana
Data de Publicação: 2018
Outros Autores: Duarte, Ana Joana, Ribeiro, Diogo, Chaves, João, Amaral, Olga, Alves, Sandra
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6259
Resumo: Brief Report
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spelling Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense TherapyCSTB geneAntisense OligonucleotidesProgressive Myoclonic Epilepsy Type 1Splicing MutationSplicing TherapiesGenética HumanaDoenças GenéticasBrief ReportUnverricht-Lundborg disease (ULD) is a common form of progressive myoclonic epilepsy caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. Presently, only pharmacological treatment and psychosocial support are available for ULD patients. To overcome the pathogenic effect of the ULD splicing mutation c.66G>A (exon 1), we investigated whether an antisense oligonucleotide therapeutic strategy could correct the defect in patient cells. A specific locked nucleic acid (LNA) antisense oligonucleotide was designed to block a cryptic 5′ss in intron 1. Overall, this approach allowed the restoration of the normal splicing pattern. Furthermore, the recovery was both sequence and dose-specific. In general, this work provides a proof of principle on the correction of a CSTB gene defect causing ULD through a mutation-specific antisense therapy. It adds evidence to the feasibility of this approach, joining the many studies that are paving the way for translating antisense technology into the clinical practice. The insights detailed herein make mutation-based therapy a clear candidate for personalized treatment of ULD patients, encouraging similar investigations into other genetic diseases.This work was funded by FCT (Fundação para a Ciência e a Tecnologia—MCTES, Portugal) project PTDC/BBB-BMD/6301/2014. Liliana Matos was grant recipient from FCT under the same projectMDPIRepositório Científico do Instituto Nacional de SaúdeMatos, LilianaDuarte, Ana JoanaRibeiro, DiogoChaves, JoãoAmaral, OlgaAlves, Sandra2019-03-21T11:52:53Z2018-09-112018-09-11T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6259engGenes (Basel). 2018 Sep 11;9(9). pii: E455. doi: 10.3390/genes90904552073-442510.3390/genes9090455info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:18Zoai:repositorio.insa.pt:10400.18/6259Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:53.508885Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
title Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
spellingShingle Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
Matos, Liliana
CSTB gene
Antisense Oligonucleotides
Progressive Myoclonic Epilepsy Type 1
Splicing Mutation
Splicing Therapies
Genética Humana
Doenças Genéticas
title_short Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
title_full Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
title_fullStr Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
title_full_unstemmed Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
title_sort Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy
author Matos, Liliana
author_facet Matos, Liliana
Duarte, Ana Joana
Ribeiro, Diogo
Chaves, João
Amaral, Olga
Alves, Sandra
author_role author
author2 Duarte, Ana Joana
Ribeiro, Diogo
Chaves, João
Amaral, Olga
Alves, Sandra
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Matos, Liliana
Duarte, Ana Joana
Ribeiro, Diogo
Chaves, João
Amaral, Olga
Alves, Sandra
dc.subject.por.fl_str_mv CSTB gene
Antisense Oligonucleotides
Progressive Myoclonic Epilepsy Type 1
Splicing Mutation
Splicing Therapies
Genética Humana
Doenças Genéticas
topic CSTB gene
Antisense Oligonucleotides
Progressive Myoclonic Epilepsy Type 1
Splicing Mutation
Splicing Therapies
Genética Humana
Doenças Genéticas
description Brief Report
publishDate 2018
dc.date.none.fl_str_mv 2018-09-11
2018-09-11T00:00:00Z
2019-03-21T11:52:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6259
url http://hdl.handle.net/10400.18/6259
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Genes (Basel). 2018 Sep 11;9(9). pii: E455. doi: 10.3390/genes9090455
2073-4425
10.3390/genes9090455
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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