Modified cyclodextrin-based nanoparticles mediated delivery of siRNA for huntingtin gene silencing across an in vitro BBB model
dc.contributor.author | Mendonça, Monique C. P. | |
dc.contributor.author | Cronin, Michael F. | |
dc.contributor.author | Cryan, John F. | |
dc.contributor.author | O'Driscoll, Caitríona M. | |
dc.contributor.funder | Science Foundation Ireland | en |
dc.contributor.funder | European Regional Development Fund | en |
dc.date.accessioned | 2021-12-02T10:51:08Z | |
dc.date.available | 2021-12-02T10:51:08Z | |
dc.date.issued | 2021-11-15 | |
dc.date.updated | 2021-12-01T14:17:11Z | |
dc.description.abstract | Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene, leading to a toxic version of the HTT protein. There are currently no disease-modifying therapies available. In this scenario, gene-based treatments for HD aimed at lowering HTT levels have become one of the most promising emerging therapeutic options. To date, however, promising results have only been achieved following direct intrathecal or intracranial injections designed to circumvent the blood-brain barrier (BBB). Consequently, efforts to develop less invasive delivery platforms are highly desirable. Here, we described a novel delivery system based on modified cyclodextrin nanoparticles (CDs) loaded with small interfering RNAs (siRNAs) targeting HTT and complexed with the rabies virus glycoprotein (RVG), a BBB-shuttle peptide. Results using an in vitro BBB model, indicate the formulation successfully crosses the brain endothelial cells, releases the encapsulated siRNAs into the cytoplasm of neuronal cells, and mediates downregulation of HTT. In conclusion, the CD platform is a promising option for delivery of siRNA-based therapeutics for HD with wider potential to treat other diseases with a genetically validated target in the central nervous system. | en |
dc.description.sponsorship | Science Foundation Ireland (SFI) and the European Regional Development Fund (ERDF) (under grant number 13/RC/2073_2 (Centre for Research in Medical Devices, CÚRAM)) | en |
dc.description.status | Peer reviewed | en |
dc.description.version | Accepted Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.citation | Mendonça, M., Cronin, M., Cryan, J. and O'Driscoll, C., (2021) ‘Modified cyclodextrin-based nanoparticles mediated delivery of siRNA for huntingtin gene silencing across an in vitro BBB model’, European Journal of Pharmaceutics and Biopharmaceutics, 169, pp. 309-318. doi: 10.1016/j.ejpb.2021.11.003 | en |
dc.identifier.doi | 10.1016/j.ejpb.2021.11.003 | en |
dc.identifier.endpage | 318 | en |
dc.identifier.issn | 0939-6411 | |
dc.identifier.journaltitle | European Journal Of Pharmaceutics And Biopharmaceutics | en |
dc.identifier.startpage | 309 | en |
dc.identifier.uri | https://hdl.handle.net/10468/12299 | |
dc.identifier.volume | 169 | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.relation.project | info:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/ | en |
dc.relation.uri | https://www.sciencedirect.com/science/article/pii/S0939641121002769 | |
dc.rights | © 2021 Elsevier B.V. This manuscript version is made available under the CC BY-NC-ND 4.0 license. | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
dc.subject | Huntington's disease | en |
dc.subject | Nanocarriers | en |
dc.subject | Non-viral gene therapy | en |
dc.subject | RVG | en |
dc.subject | Targeted cyclodextrins | en |
dc.title | Modified cyclodextrin-based nanoparticles mediated delivery of siRNA for huntingtin gene silencing across an in vitro BBB model | en |
dc.type | Article (peer-reviewed) | en |
Files
License bundle
1 - 1 of 1
Loading...
- Name:
- license.txt
- Size:
- 2.71 KB
- Format:
- Item-specific license agreed upon to submission
- Description: