Splicing Modulation as a Promising Therapeutic Strategy for Lysosomal Storage Disorders: The Mucopolysaccharidoses Example
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
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. |
id |
RCAP_9074c2d75bd1bba218d6e82487171275 |
---|---|
oai_identifier_str |
oai:repositorio.insa.pt:10400.18/8460 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1799132176736845824 |