Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery

Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery
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DOI:
10.1038/sj.gt.3302910
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发表时间:
2007-04-01
期刊:
影响因子:
5.1
通讯作者:
Harashima, H.
Harashima, H.
中科院分区:
医学3区
文献类型:
--
作者:
Khalil, I. A.;Kogure, K.;Harashima, H.

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本研究描述了一种多功能的病毒型纳米器件(MEND),它基于一种新的包装策略模仿病毒型病毒。MEND颗粒含有包装在用八精氨酸肽修饰的脂质包膜中的DNA核心。该肽通过巨胞饮介导内化,从而避免溶酶体降解。MEND介导的荧光素酶表达质粒的转染实现了与腺病毒介导的转染相当的效率,具有较低的相关细胞毒性。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是一种有前途的非病毒基因递送系统,可以提供优于现有非病毒基因递送技术的结果。
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.