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Issue 4, 2017
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Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA

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Abstract

Tools for editing the genome and epigenome have revolutionised the field of molecular biology and represent a new frontier in targeted therapeutic intervention. Although efficiencies and specificities of genome editing technologies have improved with the development of TALEs and CRISPR platforms, intracellular delivery of these larger constructs still remains a challenge using existing delivery agents. Viral vectors, including lentiviruses and adeno-associated viruses, as well as some non-viral strategies, such as cationic polymers and liposomes, are limited by packaging capacity, poor delivery, toxicity, and immunogenicity. We report a highly controlled synthetic strategy to engineer a flexible dendritic polymer using click chemistry to overcome the aforementioned delivery challenges associated with genome engineering technologies. Using a systematic approach, we demonstrate that high transfection efficiencies and packaging capacity can be achieved using this non-viral delivery methodology to deliver zinc fingers, TALEs and CRISPR/dCas9 platforms.

Graphical abstract: Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA

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Supplementary files

Article information


Submitted
09 Jan 2017
Accepted
26 Jan 2017
First published
27 Jan 2017

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2017,8, 2923-2930
Article type
Edge Article

Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA

J. A. Kretzmann, D. Ho, C. W. Evans, J. H. C. Plani-Lam, B. Garcia-Bloj, A. E. Mohamed, M. L. O'Mara, E. Ford, D. E. K. Tan, R. Lister, P. Blancafort, M. Norret and K. S. Iyer, Chem. Sci., 2017, 8, 2923
DOI: 10.1039/C7SC00097A

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