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Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach

2020-08-10Journal article Open access
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dc.contributor.authorCoutinho, Maria Francisca
dc.contributor.authorSantos, Juliana Inês
dc.contributor.authorMendonça, Liliana S.
dc.contributor.authorMatos, Liliana
dc.contributor.authorPrata, Maria João
dc.contributor.authorJurado, Amália S.
dc.contributor.authorPedroso de Lima, Maria C.
dc.contributor.authorAlves, Sandra
dc.date.accessioned2021-03-09T17:46:54Z
dc.date.available2021-03-09T17:46:54Z
dc.date.issued2020-08-10
dc.descriptionReviewpt_PT
dc.description.abstractMore 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.pt_PT
dc.description.sponsorshipThis 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/04242/2017pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2020 Aug 10;21(16):5732. doi: 10.3390/ijms21165732.pt_PT
dc.identifier.doi10.3390/ijms21165732pt_PT
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10400.18/7380
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationCEECIND/04242/2017pt_PT
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/21/16/5732pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectRNA Interference (RNAi)pt_PT
dc.subjectLysosomal Storage Diseases (LSDs)pt_PT
dc.subjectsiRNA Nanodelivery Systemspt_PT
dc.subjectStable Nucleic Acid Lipid Particles (SNALPs)pt_PT
dc.subjectSubstrate Reduction Therapy (SRT)pt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleLysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approachpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04539%2F2020/PT
oaire.citation.issue16pt_PT
oaire.citation.startPage5732pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume21pt_PT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com página web do editor da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication1ccb5f8f-0639-4328-8585-3d07f4854b0f
relation.isProjectOfPublication.latestForDiscovery1ccb5f8f-0639-4328-8585-3d07f4854b0f

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