Cited by 127RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryDendrimers and Hyperbranched Polymers

Self-assembling modified β-cyclodextrin nanoparticles as neuronal sirna delivery vectors: focus on huntington’s disease.

Godinho, Bruno M. D. C., Ogier, Julien R., Darcy, Raphael, O’Driscoll, Caitriona M., Cryan, John F.·2013·Molecular Pharmaceutics

Abstract

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disease caused by the expression of a toxic Huntingtin (HTT) protein. The use of short interfering RNAs (siRNAs) to silence the mutant protein is one of the most promising therapeutic strategies under investigation. The biggest caveat to siRNA-based approaches is the lack of efficient and nontoxic delivery vectors for siRNA delivery to the central nervous system. In this study, we investigated the potential of modified amphiphilic β-cyclodextrins (CDs), oligosaccharide-based molecules, as novel siRNA neuronal carriers. We show that CDs formed nanosize particles which were stable in artificial cerebrospinal fluid. Moreover, these complexes were able to reduce the expression of the HTT gene in rat striatal cells (ST14A-HTT120Q) and in human HD primary fibroblasts. Only limited toxicity was observed with CD·siRNA nanoparticles in any of the in vitro models used. Sustained knockdown effects were observed in the striatum of the R6/2 mouse model of HD after single direct injections of CD·siRNA nanoparticles. Repeated brain injections of CD·siRNA complexes resulted in selective alleviation of motor deficits in this mouse model. Together these data support the utility of modified β-CDs as efficient and safe siRNA delivery vectors for RNAi-based therapies for neuropsychiatric and neurodegenerative disorders.

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Crossref · 10.1021/mp3003946

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  • siRNA encapsulated cyclodextrin nanoparticles reduce expression of huntingtin mRNA both in vivo and in vitro.

    “short-interfering RNA (siRNA) encapsulated cyclodextrin nanoparticles were found capable to reduce expression of HTT mRNA both in vivo as well as in vitro”

    From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Godinho et al., 2013

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Authors
Godinho, B. M. D. C., Ogier, J. R., Darcy, R., O’Driscoll, C. M., & Cryan, J. F.
Affiliations
  • University College Cork (IE)
  • University College Dublin (IE)
  • Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland
Corresponding author
Cryan, John F.
Venue
Molecular Pharmaceutics
Published
2013-01-09
Volume
10
Issue
2
Pages
640-649
ISSN
  • 1543-8384 (ISSN-L)
  • 1543-8392
OpenAlex
W2064441112
Cited by
126
References
52
Citations by year
2026: 4 · 2025: 11 · 2024: 12 · 2023: 8 · 2022: 7 · 2021: 14 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 10 · 2016: 5 · 2015: 12 · 2014: 11 · 2013: 10
FWCI
4.24
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
Huntington's disease, siRNA delivery, modified β-cyclodextrin, RNAi therapy, brain drug delivery, striatal cells, R6/2 mouse model, motor impairment, nanoparticle toxicity
MeSH terms
Animals, Cells, Cultured, Genetic Vectors, Humans, Huntington Disease, Genetic Therapy, Neurodegenerative Diseases, RNA, Small Interfering, beta-Cyclodextrins, Mice, Rats, Nanoparticles

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