Covalent recruitment of polymers and nanoparticles onto glycan-engineered cells enhances gene delivery during short
Qiao Tang1,2,3, Ruben M F Tomás4,3, Matthew I Gibson1,4,2,5
1Department of Chemistry, University of Warwick Gibbet Hill Road Coventry CV4 7AL UK matt.gibson@manchester.ac.uk.
Abstract:
Non-viral gene delivery with cationic polymers/nanoparticles relies on iterative optimization of the carrier to achieve delivery. Here we demonstrate, instead, that precision engineering of cell surfaces to covalently capture a polyplex accelerates gene delivery within just 10 min of exposure. Azides were installed into cell-surface sialic acids, which enabled the rapid and selective recruitment of cyclooctyne-functional polyplexes, leading to increased delivery of fluorescent cargo, and also increased plasmid expression and siRNA knockdown. Covalent delivery enhancement was also shown for a polymer-coated nanoparticle delivery system. This validates using cellular metabolic engineering (or other synthetic biology) tools to overcome payload delivery challenges.
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