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

Show simple item record O'Mahony, Aoife M. Godinho, Bruno M. D. C. Ogier, Julien R. Devocelle, Marc Darcy, Raphael Cryan, John F. O'Driscoll, Caitríona M. 2013-01-09T11:51:19Z 2012-08-03
dc.identifier.citation O'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/cn3000372 en
dc.identifier.volume 10 en
dc.identifier.issued 3 en
dc.identifier.startpage 744 en
dc.identifier.endpage 752 en
dc.identifier.issn 1948-7193
dc.identifier.doi 10.1021/cn3000372
dc.description.abstract RNA 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.sponsorship Science Foundation Ireland (grant no. 07/SRC/B115); Irish Research Council for Science Engineering and Technology (Embark initiative) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher American Chemical Society en
dc.rights Copyright © 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 en
dc.subject siRNA en
dc.subject Nanotechnology en
dc.subject Click chemistry en
dc.subject Neurons en
dc.subject Gene knockdown en
dc.subject.lcsh Cyclodextrins en
dc.title Click-modified cyclodextrins as non-viral vectors for neuronal siRNA delivery en
dc.type Article (peer-reviewed) en
dc.internal.authorurl en
dc.internal.authorcontactother Caitriona O'Driscoll, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: en
dc.internal.availability Full text available en 2013-01-04T14:54:51Z
dc.description.version Accepted Version en
dc.internal.rssid 184533869
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Drug Delivery Network en
dc.contributor.funder Irish Research Council for Science Engineering and Technology en
dc.description.status Peer reviewed en
dc.identifier.journaltitle ACS Chemical Neuroscience en
dc.internal.copyrightchecked Yes - ROMEO - ACS policy. Accepted Version and Embargo 12 months. en
dc.internal.licenseacceptance Yes en
dc.internal.placepublication Washington, D.C. en
dc.internal.IRISemailaddress en

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