Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example

Detalhes bibliográficos
Autor(a) principal: Santos, Juliana Inês
Data de Publicação: 2022
Outros Autores: Gonçalves, Mariana, Matos, Liliana, Moreira, Luciana, Carvalho, Sofia, Prata, Maria João, Coutinho, Maria Francisca, 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/10400.18/8460
Resumo: This article belongs to the Special Issue New Insights into Lysosomal Storage Disorders and Other Rare Genetic Diseases.
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spelling Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses ExampleLysosomal Storage DiseasesMucopolysaccharidosesRNASplicingAntisense OligonucleotidesU1 snRNA (small nuclear RNA)Splice-switching OligonucleotidesRNA-based TherapiesDoenças GenéticasGenética HumanaThis article belongs to the Special Issue New Insights into Lysosomal Storage Disorders and Other Rare Genetic Diseases.Over recent decades, the many functions of RNA have become more evident. This molecule has been recognized not only as a carrier of genetic information, but also as a specific and essential regulator of gene expression. Different RNA species have been identified and novel and exciting roles have been unveiled. Quite remarkably, this explosion of novel RNA classes has increased the possibility for new therapeutic strategies that tap into RNA biology. Most of these drugs use nucleic acid analogues and take advantage of complementary base pairing to either mimic or antagonize the function of RNAs. Among the most successful RNA-based drugs are those that act at the pre-mRNA level to modulate or correct aberrant splicing patterns, which are caused by specific pathogenic variants. This approach is particularly tempting for monogenic disorders with associated splicing defects, especially when they are highly frequent among affected patients worldwide or within a specific population. With more than 600 mutations that cause disease affecting the pre-mRNA splicing process, we consider lysosomal storage diseases (LSDs) to be perfect candidates for this type of approach. Here, we introduce the overall rationale and general mechanisms of splicing modulation approaches and highlight the currently marketed formulations, which have been developed for non-lysosomal genetic disorders. We also extensively reviewed the existing preclinical studies on the potential of this sort of therapeutic strategy to recover aberrant splicing and increase enzyme activity in our diseases of interest: the LSDs. Special attention was paid to a particular subgroup of LSDs: the mucopolysaccharidoses (MPSs). By doing this, we hoped to unveil the unique therapeutic potential of the use of this sort of approach for LSDs as a whole.This research was partially funded by the FCT (FCT/PTDC/BBB-BMD/6301/2014 and EXPL/BTM-SAL/0659/2021), the Portuguese Society for Metabolic Disorders (Sociedade Portuguesa de Doenças Metabólicas, SPDM—Bolsa SPDM de apoio à investigação Dr Aguinaldo Cabral 2018 (2019DGH1629/SPDM2018I&D) and 2019 (2020DGH1834)), the Sanfilippo Children’s Foundation (SCF Incubator Grant 2019: 2019DGH1656/SCF2019I&D) and the MPS Society (2019DGH1642).MDPIRepositório Científico do Instituto Nacional de SaúdeSantos, Juliana InêsGonçalves, MarianaMatos, LilianaMoreira, LucianaCarvalho, SofiaPrata, Maria JoãoCoutinho, Maria FranciscaAlves, Sandra2023-01-26T15:12:30Z2022-04-192022-04-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8460engLife (Basel). 2022 Apr 19;12(5):608. doi: 10.3390/life12050608. Review2075-172910.3390/life12050608info: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:RCAAP2023-07-20T15:42:35Zoai:repositorio.insa.pt:10400.18/8460Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:43:05.788729Repositório 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 Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
title Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
spellingShingle Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
Santos, Juliana Inês
Lysosomal Storage Diseases
Mucopolysaccharidoses
RNA
Splicing
Antisense Oligonucleotides
U1 snRNA (small nuclear RNA)
Splice-switching Oligonucleotides
RNA-based Therapies
Doenças Genéticas
Genética Humana
title_short Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
title_full Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
title_fullStr Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
title_full_unstemmed Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
title_sort Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
author Santos, Juliana Inês
author_facet Santos, Juliana Inês
Gonçalves, Mariana
Matos, Liliana
Moreira, Luciana
Carvalho, Sofia
Prata, Maria João
Coutinho, Maria Francisca
Alves, Sandra
author_role author
author2 Gonçalves, Mariana
Matos, Liliana
Moreira, Luciana
Carvalho, Sofia
Prata, Maria João
Coutinho, Maria Francisca
Alves, Sandra
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Santos, Juliana Inês
Gonçalves, Mariana
Matos, Liliana
Moreira, Luciana
Carvalho, Sofia
Prata, Maria João
Coutinho, Maria Francisca
Alves, Sandra
dc.subject.por.fl_str_mv Lysosomal Storage Diseases
Mucopolysaccharidoses
RNA
Splicing
Antisense Oligonucleotides
U1 snRNA (small nuclear RNA)
Splice-switching Oligonucleotides
RNA-based Therapies
Doenças Genéticas
Genética Humana
topic Lysosomal Storage Diseases
Mucopolysaccharidoses
RNA
Splicing
Antisense Oligonucleotides
U1 snRNA (small nuclear RNA)
Splice-switching Oligonucleotides
RNA-based Therapies
Doenças Genéticas
Genética Humana
description This article belongs to the Special Issue New Insights into Lysosomal Storage Disorders and Other Rare Genetic Diseases.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-19
2022-04-19T00:00:00Z
2023-01-26T15:12:30Z
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/10400.18/8460
url http://hdl.handle.net/10400.18/8460
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Life (Basel). 2022 Apr 19;12(5):608. doi: 10.3390/life12050608. Review
2075-1729
10.3390/life12050608
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
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