Virus-Inspired Polymer for Efficient In Vitro and In Vivo Gene Delivery

被引:106
作者
Cheng, Yilong [1 ,2 ]
Yumul, Roma C. [1 ,2 ]
Pun, Suzie H. [1 ,2 ]
机构
[1] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[2] Univ Washington, Mol Engn & Sci Inst, Seattle, WA 98195 USA
关键词
DNA release; gene delivery; melittin; VIPER; virus-inspired polymers; SIRNA DELIVERY; MEMBRANE PENETRATION; PLASMID DNA; VECTORS; ADENOVIRUS; CELLS; NANOPARTICLES; THERAPEUTICS; POLYPLEXES; PEPTIDES;
D O I
10.1002/anie.201605958
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:12013 / 12017
页数:5
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