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Issue 22, 2020

Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers

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Abstract

Gene delivery has become the focus of clinical treatments, thus motivating delivery strategies that are capable of targeting certain cell types in the context of both vaccines and therapeutics. Here, we present a gene delivery platform enabled by host–guest interaction between a cyclodextrin with emanating chains of cationic polymers, poly(2-dimethylaminoethyl meth-acrylate) (PDMAEMA) paired with a glycosylated adamantane containing copolymer. By decoupling the cationic polymer and glycosylation chemistries, we were able to vary each independently to study the transfection efficiency both in vitro and ex vivo in human skin explants. Medium length PDMAEMA enabled optimal DNA complexation, and glycosylation specifically enhanced the number of cells transfected 100-fold in vitro and 3-fold ex vivo. Furthermore, these glycopolymers enabled greater immune cell up take, specifically in skin resident leukocytes. This platform is a facile and clinically translatable way to study how glycosylation affects cellular uptake and targeting in a complex cellular medium.

Graphical abstract: Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers

Supplementary files

Article information


Submitted
27 Mar 2020
Accepted
03 May 2020
First published
12 May 2020

Polym. Chem., 2020,11, 3768-3774
Article type
Paper

Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers

A. K. Blakney, R. Liu, G. Yilmaz, Y. Abdouni, P. F. McKay, C. R. Bouton, R. J. Shattock and C. R. Becer, Polym. Chem., 2020, 11, 3768 DOI: 10.1039/D0PY00449A

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