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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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Publication details

The article was received on 09 Jan 2017, accepted on 26 Jan 2017 and first published on 27 Jan 2017


Article type: Edge Article
DOI: 10.1039/C7SC00097A
Citation: Chem. Sci., 2017,8, 2923-2930
  • Open access: Creative Commons BY license
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    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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