Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| 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/10400.18/7380 |
Resumo: | Review |
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Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic ApproachRNA Interference (RNAi)Lysosomal Storage Diseases (LSDs)siRNA Nanodelivery SystemsStable Nucleic Acid Lipid Particles (SNALPs)Substrate Reduction Therapy (SRT)Doenças GenéticasReviewMore than two thirds of Lysosomal Storage Diseases (LSDs) present central nervous system involvement. Nevertheless, only one of the currently approved therapies has an impact on neuropathology. Therefore, alternative approaches are under development, either addressing the underlying enzymatic defect or its downstream consequences. Also under study is the possibility to block substrate accumulation upstream, by promoting a decrease of its synthesis. This concept is known as substrate reduction therapy and may be triggered by several molecules, such as small interfering RNAs (siRNAs). siRNAs promote RNA interference, a naturally occurring sequence-specific post-transcriptional gene-silencing mechanism, and may target virtually any gene of interest, inhibiting its expression. Still, naked siRNAs have limited cellular uptake, low biological stability, and unfavorable pharmacokinetics. Thus, their translation into clinics requires proper delivery methods. One promising platform is a special class of liposomes called stable nucleic acid lipid particles (SNALPs), which are characterized by high cargo encapsulation efficiency and may be engineered to promote targeted delivery to specific receptors. Here, we review the concept of SNALPs, presenting a series of examples on their efficacy as siRNA nanodelivery systems. By doing so, we hope to unveil the therapeutic potential of these nanosystems for targeted brain delivery of siRNAs in LSDs.This work was supported by 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 Sanfilippo Children’s Foundation (SCF Incubator Grant 2019; 2019DGH1656/SCF2019I&D). Additional support came from the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme (project CENTRO-01-0145-FEDER-000008: BrainHealth 2020), and the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia (projects POCI-01-0145-FEDER-016390: CANCEL STEM and POCI-01-0145-FEDER-007440; UIDB/04539/2020). L.S.M. is funded by FCT/MCTES National Funds under project CEECIND/04242/2017MDPIRepositório Científico do Instituto Nacional de SaúdeCoutinho, Maria FranciscaSantos, Juliana InêsMendonça, Liliana S.Matos, LilianaPrata, Maria JoãoJurado, Amália S.Pedroso de Lima, Maria C.Alves, Sandra2021-03-09T17:46:54Z2020-08-102020-08-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7380engInt J Mol Sci. 2020 Aug 10;21(16):5732. doi: 10.3390/ijms21165732.1661-659610.3390/ijms21165732info: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:RCAAP2023-07-20T15:41:59Zoai:repositorio.insa.pt:10400.18/7380Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:02.599800Repositório 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 |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| title |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| spellingShingle |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach Coutinho, Maria Francisca RNA Interference (RNAi) Lysosomal Storage Diseases (LSDs) siRNA Nanodelivery Systems Stable Nucleic Acid Lipid Particles (SNALPs) Substrate Reduction Therapy (SRT) Doenças Genéticas |
| title_short |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| title_full |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| title_fullStr |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| title_full_unstemmed |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| title_sort |
Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach |
| author |
Coutinho, Maria Francisca |
| author_facet |
Coutinho, Maria Francisca Santos, Juliana Inês Mendonça, Liliana S. Matos, Liliana Prata, Maria João Jurado, Amália S. Pedroso de Lima, Maria C. Alves, Sandra |
| author_role |
author |
| author2 |
Santos, Juliana Inês Mendonça, Liliana S. Matos, Liliana Prata, Maria João Jurado, Amália S. Pedroso de Lima, Maria C. 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 |
Coutinho, Maria Francisca Santos, Juliana Inês Mendonça, Liliana S. Matos, Liliana Prata, Maria João Jurado, Amália S. Pedroso de Lima, Maria C. Alves, Sandra |
| dc.subject.por.fl_str_mv |
RNA Interference (RNAi) Lysosomal Storage Diseases (LSDs) siRNA Nanodelivery Systems Stable Nucleic Acid Lipid Particles (SNALPs) Substrate Reduction Therapy (SRT) Doenças Genéticas |
| topic |
RNA Interference (RNAi) Lysosomal Storage Diseases (LSDs) siRNA Nanodelivery Systems Stable Nucleic Acid Lipid Particles (SNALPs) Substrate Reduction Therapy (SRT) Doenças Genéticas |
| description |
Review |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-08-10 2020-08-10T00:00:00Z 2021-03-09T17:46:54Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/7380 |
| url |
http://hdl.handle.net/10400.18/7380 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Int J Mol Sci. 2020 Aug 10;21(16):5732. doi: 10.3390/ijms21165732. 1661-6596 10.3390/ijms21165732 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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