CELLULAR UPTAKE OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES AND THEIR ANALOGS

被引：91

作者：

TEMSAMANI, J ^{[1
]}

KUBERT, M ^{[1
]}

TANG, JY ^{[1
]}

PADMAPRIYA, A ^{[1
]}

AGRAWAL, S ^{[1
]}

机构：

[1] HYBRIDON INC, 1 INNOVAT DR, WORCESTER, MA 01605 USA

来源：

ANTISENSE RESEARCH AND DEVELOPMENT | 1994年 / 4卷 / 01期

关键词：

D O I：

10.1089/ard.1994.4.35

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The uptake and intracellular distribution of oligonucleotide phosphorothioates (S-oligonucleotides) and their analogs by various cells lines were studied using internally S-35-labeled oligonucleotides. Intracellular accumulation starts in the first 2 hr and reaches a maximum at about 16 hr. A decrease of intracellular concentration of the S-oligonucleotide was observed after 16 hr, probably due to a significant efflux transport. Cellular uptake was dependent on the extracellular concentration. The intracellular concentration was significantly higher than that in the medium. The uptake and the intracellular distribution were different in the various cell tines studied. Comparative studies of the uptake of the S-oligonucleotide and various 3' end-modified S-oligonucleotides show that end modified S-oligonucleotides with a hydrophobic group significantly increases the uptake. The introduction of methylphosphonothioate linkages at the 3' end of the S-oligonucleotide also resulted in an increase in uptake.

引用

页码：35 / 42

页数：8

共 36 条

[1] PHARMACOKINETICS, BIODISTRIBUTION, AND STABILITY OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES IN MICE [J].