CATIONIC LIPIDS IMPROVE ANTISENSE OLIGONUCLEOTIDE UPTAKE AND PREVENT DEGRADATION IN CULTURED-CELLS AND IN HUMAN SERUM

被引：161

作者：

CAPACCIOLI, S ^{[1
]}

DIPASQUALE, G ^{[1
]}

MINI, E ^{[1
]}

MAZZEI, T ^{[1
]}

QUATTRONE, A ^{[1
]}

机构：

[1] DEPT PHARMACOL, I-50134 FLORENCE, ITALY

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1993年 / 197卷 / 02期

关键词：

D O I：

10.1006/bbrc.1993.2552

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

The power of antisense phosphodiester oligonucleotides (aODN) as regulatory molecules of gene expression is strongly limited by their low cellular uptake and very rapid nuclease-mediated degradation. This study deals with the effect of artificial cationic lipids on ODN cellular uptake and degradation in cell cultures and in human serum. At the ODN levels normally used in antisense-mediated gene regulation experiments, a cationic lipid, DOTAP, enhances the rate of ODN uptake more than 25 fold, but at lower ODN levels the effect of DOTAP is absent. These findings are consistent with a mechanism of ODN internalization by receptor-mediated saturable endocytosis that is bypassed by DOTAP. ODN degradation by nucleases is markedly prevented by DOTAP both in cultured cells and in human serum. Other cationic lipids, namely DOTMA and DOGS, exhibit very similar behaviour. The relatively slight cellular toxicity revealed by cationic lipids contribute to render these molecules very suitable for aODN vehiculation. © 1993 Academic Press. All rights reserved.

引用

页码：818 / 825

页数：8

共 39 条

[1]

INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS IN EARLY INFECTED AND CHRONICALLY INFECTED-CELLS BY ANTISENSE OLIGODEOXYNUCLEOTIDES AND THEIR PHOSPHOROTHIOATE ANALOGS [J].