Advances in the design of (nano)formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous system

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dc.contributor.authorMendonça, Monique C. P.
dc.contributor.authorKont, Ayse
dc.contributor.authorAburto, Maria Rodriguez
dc.contributor.authorCryan, John F.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEuropean Regional Development Funden
dc.date.accessioned2021-10-08T09:24:25Z
dc.date.available2021-10-08T09:24:25Z
dc.date.issued2021-03-18
dc.date.updated2021-10-07T12:48:57Z
dc.description.abstractRNA-based therapeutics have emerged as one of the most powerful therapeutic options used for the modulation of gene/protein expression and gene editing with the potential to treat neurodegenerative diseases. However, the delivery of nucleic acids to the central nervous system (CNS), in particular by the systemic route, remains a major hurdle. This review will focus on the strategies for systemic delivery of therapeutic nucleic acids designed to overcome these barriers. Pathways and mechanisms of transport across the blood-brain barrier which could be exploited for delivery are described, focusing in particular on smaller nucleic acids including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA). Approaches used to enhance delivery including chemical modifications, nanocarrier systems, and target selection (cell-specific delivery) are critically analyzed. Learnings achieved from a comparison of the successes and failures reported for CNS delivery of ASOs versus siRNA will help identify opportunities for a wider range of nucleic acids and accelerate the clinical translation of these innovative therapies.en
dc.description.sponsorshipScience Foundation Ireland and the European Regional Development Fund (Grant 13/RC/2073_2); Science Foundation Ireland (17/RC-PhD/3477; 12/RC/2278_P2)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMendonça, M. C. P., Kont, A., Aburto, M. R., Cryan, J. F. and O'Driscoll, C. M. (2021) 'Advances in the design of (nano)formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous system', Molecular Pharmaceutics, 18(4), pp.1491-1506. doi: 10.1021/acs.molpharmaceut.0c01238en
dc.identifier.doi10.1021/acs.molpharmaceut.0c01238en
dc.identifier.eissn1543-8392
dc.identifier.endpage1506en
dc.identifier.issn1543-8384
dc.identifier.issued4en
dc.identifier.journaltitleMolecular Pharmaceuticsen
dc.identifier.startpage1491en
dc.identifier.urihttps://hdl.handle.net/10468/12068
dc.identifier.volume18en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.rights© 2021, American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, after technical editing by the publisher. To access the final edited and published work see: https://doi.org/10.1021/acs.molpharmaceut.0c01238en
dc.subjectAntisense oligonucleotideen
dc.subjectSmall interfering RNAen
dc.subjectBlood−brain barrieren
dc.subjectSystemic deliveryen
dc.subjectNeurological diseasesen
dc.titleAdvances in the design of (nano)formulations for delivery of antisense oligonucleotides and small interfering RNA: Focus on the central nervous systemen
dc.typeArticle (peer-reviewed)en
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