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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Accepted Version
Date
2021-03-18
Authors
Mendonça, Monique C. P.
Kont, Ayse
Aburto, Maria Rodriguez
Cryan, John F.
O'Driscoll, Caitríona M.
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Published Version
Abstract
RNA-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.
Description
Keywords
Antisense oligonucleotide , Small interfering RNA , Blood−brain barrier , Systemic delivery , Neurological diseases
Citation
Mendonça, 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.0c01238
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Copyright
© 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.0c01238