A Truncated HGP Peptide Sequence That Retains Endosomolytic Activity and Improves Gene Delivery Efficiencies

被引：32

作者：

Kwon, Ester J. ^{[1
]}

Liong, Sylvie ^{[1
]}

Pun, Suzie H. ^{[1
]}

机构：

[1] Univ Washington, Ctr Bioengn, Seattle, WA 98195 USA

来源：

MOLECULAR PHARMACEUTICS | 2010年 / 7卷 / 04期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Gene delivery; peptide; polyethylenimine; INTRACELLULAR TRAFFICKING; PLASMID DNA; POLYETHYLENIMINE; PROTEIN; CELLS; TRANSFECTION; POLYPLEXES; VECTORS; CULTURE;

D O I：

10.1021/mp1000668

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

HGP is a 24-amino acid peptide derived from HIV gp41 that increases vesicular escape when incorporated into gene delivery vehicles. The typical yield of HGP from solid phase peptide synthesis is low due to its length and hydrophobicity. The goal of this work was to investigate truncated sequences that maintained activity in order to improve the ease and yield of synthesis. A shortened, 15-amino acid sequence retained comparable lytic activity and the ability to interact with lipids when compared to the full length peptide. A scrambled peptide showed poor lytic activity, confirming that the activity of these endosomal escape peptides is sequence specific. Peptides were covalently attached to polyethylenimine (PEI) and used to condense plasmid DNA to form nanoparliculate carriers. When delivery efficiencies of PEI peptide conjugates were compared in vitro, PEI modified with the truncated HGP sequence increased transgene expression over unmodified PEI and full length HGP.

引用

页码：1260 / 1265

页数：6

共 20 条

[1] Quantitative three-dimensional analysis of the intracellular trafficking of plasmid DNA transfected by a nonviral gene delivery system using confocal laser scanning microscopy [J].