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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, 21 (6). pp. 2482-2492. doi:10.1021/acs.biomac.0c00445 ISSN 1525-7797.
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WRAP-mannosylated-poly(ethylene imine)-copolymers-enhance-saRNA-uptake-expression-human-skin-explants-Becer-2020.pdf - Accepted Version - Requires a PDF viewer. Download (1798Kb) | Preview |
Official URL: http://dx.doi.org/10.1021/acs.biomac.0c00445
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 | ||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > 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: | 8 June 2020 | ||||||||||||||||||||||||
| Dates: |
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| Volume: | 21 | ||||||||||||||||||||||||
| Number: | 6 | ||||||||||||||||||||||||
| Page Range: | pp. 2482-2492 | ||||||||||||||||||||||||
| DOI: | 10.1021/acs.biomac.0c00445 | ||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||
| Reuse Statement (publisher, data, author rights): | 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 | ||||||||||||||||||||||||
| Date of first compliant deposit: | 30 April 2020 | ||||||||||||||||||||||||
| Date of first compliant Open Access: | 6 April 2021 | ||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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