Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 39, Pages 12013-12017Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201605958
Keywords
DNA release; gene delivery; melittin; VIPER; virus-inspired polymers
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Funding
- NIH [2R01NS064404]
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Clinical translation of nucleic acids drugs has been stunted by limited delivery options. Herein, we report a synthetic polymer designed to mimic viral mechanisms of delivery called VIPER (virus-inspired polymer for endosomal release). VIPER is composed of a polycation block for condensation of nucleic acids, and a pH-sensitive block for acid-triggered display of a lytic peptide to promote trafficking to the cell cytosol. VIPER shows superior efficiencies compared to commercial agents when delivering genes to multiple immortalized cell lines. Importantly, in murine models, VIPER facilitates effective gene transfer to solid tumors.
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