Click-modified cyclodextrins as non-viral vectors for neuronal siRNA delivery

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dc.contributor.authorO'Mahony, Aoife M.
dc.contributor.authorGodinho, Bruno M. D. C.
dc.contributor.authorOgier, Julien R.
dc.contributor.authorDevocelle, Marc
dc.contributor.authorDarcy, Raphael
dc.contributor.authorCryan, John F.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Drug Delivery Networken
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.date.accessioned2013-01-09T11:51:19Z
dc.date.issued2012-08-03
dc.date.updated2013-01-04T14:54:51Z
dc.description.abstractRNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors, which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified β-cyclodextrin (CD) vector was synthesised, which complexed siRNA to form cationic nanoparticles of less than 200nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalised hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labelled siRNA, whilst maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.en
dc.description.sponsorshipScience Foundation Ireland (grant no. 07/SRC/B115); Irish Research Council for Science Engineering and Technology (Embark initiative)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Mahony, A.M., Godinho, B.M.D.C., Ogier, J., Devocelle, M., Darcy, R., Cryan, J.F., O'Driscoll, C.M. (2012) 'Click-modified cyclodextrins as non-viral vectors for neuronal siRNA delivery'. ACS Chemical Neuroscience, 10 (3):744-752. doi: 10.1021/cn3000372en
dc.identifier.doi10.1021/cn3000372
dc.identifier.endpage752en
dc.identifier.issn1948-7193
dc.identifier.issued3en
dc.identifier.journaltitleACS Chemical Neuroscienceen
dc.identifier.startpage744en
dc.identifier.urihttps://hdl.handle.net/10468/871
dc.identifier.volume10en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urihttp://pubs.acs.org/journal/acncdm
dc.rightsCopyright © 2012 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/cn3000372en
dc.subjectsiRNAen
dc.subjectNanotechnologyen
dc.subjectClick chemistryen
dc.subjectNeuronsen
dc.subjectGene knockdownen
dc.subject.lcshCyclodextrinsen
dc.titleClick-modified cyclodextrins as non-viral vectors for neuronal siRNA deliveryen
dc.typeArticle (peer-reviewed)en
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