Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA

Jessica A. Kretzmann, Diwei Ho, Cameron W. Evans, Janice H C Plani-Lam, Benjamin Garcia-Bloj, A Elaaf Mohamed, Megan L. O'Mara, Ethan Ford, Dennis E. K. Tan, Ryan Lister, Pilar Blancafort, Marck Norret, K. Swaminatha Iyer

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2923-2930
Number of pages8
JournalChemical Science
Issue number4
Publication statusPublished - 27 Jan 2017


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