Khalil I A, Kogure K, Futaki S, Hama S, Akita H, Ueno M, Kishida H, Kudoh M, Mishina Y, Kataoka K, Yamada M, Harashima H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
Gene Ther. 2007 Apr;14(8):682-9. doi: 10.1038/sj.gt.3302910. Epub 2007 Feb 1.
This study describes a multifunctional envelope-type nano device (MEND) that mimics an envelope-type virus based on a novel packaging strategy. MEND particles contain a DNA core packaged into a lipid envelope modified with an octaarginine peptide. The peptide mediates internalization via macropinocytosis, which avoids lysosomal degradation. MEND-mediated transfection of a luciferase expression plasmid achieved comparable efficiency to adenovirus-mediated transfection, with lower associated cytotoxicity. Furthermore, topical application of MEND particles containing constitutively active bone morphogenetic protein (BMP) type IA receptor (caBmpr1a) gene had a significant impact on hair growth in vivo. These data demonstrate that MEND is a promising non-viral gene delivery system that may provide superior results to existing non-viral gene delivery technologies.
本研究描述了一种基于新型包装策略、模仿包膜型病毒的多功能包膜型纳米装置(MEND)。MEND颗粒包含一个包装在经八聚精氨酸肽修饰的脂质包膜内的DNA核心。该肽通过巨胞饮作用介导内化,从而避免溶酶体降解。MEND介导的荧光素酶表达质粒转染效率与腺病毒介导的转染相当,且细胞毒性较低。此外,局部应用含有组成型活性骨形态发生蛋白(BMP)IA型受体(caBmpr1a)基因的MEND颗粒对体内毛发生长有显著影响。这些数据表明,MEND是一种有前景的非病毒基因递送系统,可能比现有的非病毒基因递送技术提供更优异的结果。