Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants
Autor: | Yamin Abdouni, Robin J. Shattock, Clément R. Bouton, Gokhan Yilmaz, Anna K. Blakney, C. Remzi Becer, Renjie Liu, Paul F. McKay |
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Jazyk: | angličtina |
Předmět: |
Glycosylation
Polymers and Plastics Glycopolymer Bioengineering 02 engineering and technology macromolecular substances 010402 general chemistry Transfection 01 natural sciences Polyethylene Glycols Biomaterials chemistry.chemical_compound Materials Chemistry Humans Messenger RNA Chemistry RNA 021001 nanoscience & nanotechnology QP In vitro 3. Good health 0104 chemical sciences Cell biology carbohydrates (lipids) Mannosylation Imines Polyethylenes 0210 nano-technology saRNA Ex vivo |
Zdroj: | Biomacromolecules |
ISSN: | 1526-4602 1525-7797 |
DOI: | 10.1021/acs.biomac.0c00445 |
Popis: | 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. |
Databáze: | OpenAIRE |
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