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Mannosylated poly(ethylene imine) copolymers enhance saRNA uptake and expression in human skin explants

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Blakney, Anna K., Abdouni, Yamin, Yilmaz, Gokhan, Liu, Renjie, McKay, Paul F., Bouton, Clément R., Shattock, Robin J. and Becer, C. Remzi (2020) Mannosylated poly(ethylene imine) copolymers enhance saRNA uptake and expression in human skin explants. Biomacromolecules . doi:10.1021/acs.biomac.0c00445 (In Press)

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WRAP-mannosylated-poly(ethylene imine)-copolymers-enhance-saRNA-uptake-expression-human-skin-explants-Becer-2020.pdf - Accepted Version
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Official URL: http://dx.doi.org/10.1021/acs.biomac.0c00445

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Abstract

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host–guest interaction between cyclodextrin and adamantane. We show that the host–guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Messenger RNA, RNA -- Structure, Vaccines, Skin -- Cultures , Mannose
Journal or Publication Title: Biomacromolecules
Publisher: American Chemical Society
ISSN: 1525-7797
Official Date: 6 April 2020
Dates:
DateEvent
6 April 2020Published
6 April 2020Accepted
Date of first compliant deposit: 30 April 2020
DOI: 10.1021/acs.biomac.0c00445
Status: Peer Reviewed
Publication Status: In Press
Publisher Statement: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.biomac.0c00445
Access rights to Published version: Restricted or Subscription Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDWhitaker Foundationhttp://viaf.org/viaf/137088448
794059H2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665
UNSPECIFIEDGreat Britain. Department of Healthhttp://viaf.org/viaf/134415268
EP/R013764/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
642083H2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665
UNSPECIFIEDChina Scholarship Councilhttp://dx.doi.org/10.13039/501100004543
UNSPECIFIEDUniversity of London. Queen Maryhttp://viaf.org/viaf/141388772

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