A pH-sensitive polymer that enhances cationic lipid-mediated gene transfer

被引：137

作者：

Cheung, CY ^{[1
]}

Murthy, N ^{[1
]}

Stayton, PS ^{[1
]}

Hoffman, AS ^{[1
]}

机构：

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

来源：

BIOCONJUGATE CHEMISTRY | 2001年 / 12卷 / 06期

关键词：

D O I：

10.1021/bc0100408

中图分类号：

Q5 [生物化学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

The efficient release of nonviral gene carriers from endosomes is an important step for the successful delivery of DNA into the cell nucleus. A synthetic pH-sensitive anionic polymer, poly(propylacrylic acid) (PPAA), was designed to aid in endosomal escape of nonviral vectors and improve the transfection efficiencies with these vectors. Transfection of NIH3T3 fibroblasts with ternary physical mixtures of the cationic lipid DOTAP, pCMV beta plasmid DNA, and PPAA showed marked enhancement of both gene expression levels and fraction of cells transfected compared to binary control mixtures of DOTAP and DNA. PPAA also significantly improved the serum-stability of DOTAP/DNA vectors. The DOTAP/DNA/PPAA vectors maintained high levels of transfection in media containing up to 50% serum. The striking enhancement of transfection efficiency with cationic lipid/DNA/PPAA mixtures, along with the enhanced serum-stability, suggests that PPAA may provide significant improvements for the in vivo intracellular delivery of drugs such as DNA, oligonucleotides, proteins, and peptides.

引用

页码：906 / 910

页数：5

共 34 条

[1]

Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease [J].