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Title: Lysosomal Storage Disease-Associated Neuropathy: Targeting Stable Nucleic Acid Lipid Particle (SNALP)-Formulated siRNAs to the Brain as a Therapeutic Approach
Authors: Coutinho, Maria Francisca
Santos, Juliana Inês
Mendonça, Liliana 
Matos, Liliana
Prata, Maria João 
Jurado, Amália 
Lima, Maria C. Pedroso de 
Alves, Sandra
Keywords: lysosomal storage diseases (LSDs); neuropathy; substrate reduction therapy (SRT); RNA interference (RNAi); siRNA nanodelivery systems; stable nucleic acid lipid particles (SNALPs)
Issue Date: 10-Aug-2020
Publisher: MDPI
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 21
Issue: 16
Abstract: More 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.
ISSN: 1422-0067
DOI: 10.3390/ijms21165732
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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