Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication

被引：23

作者：

Elmén, J

Zhang, HY

Zuber, B

Ljungberg, K

Wahren, B

Wahlestedt, C

Liang, ZC

机构：

[1] Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Swedish Inst Infect Dis Control, Dept Virol, S-17182 Solna, Sweden

来源：

FEBS LETTERS | 2004年 / 578卷 / 03期

关键词：

LNA; antisense; RNase H; HIV; dimerization initiation site;

D O I：

10.1016/j.febslet.2004.11.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have evaluated antisense design and efficacy of locked nucleic acid (LNA) and DNA oligonucleotide (ON) mix-mers targeting the conserved HIV-1 dimerization initiation site (DIS). LNA is a high affinity nucleotide analog, nuclease resistant and elicits minimal toxicity. We show that inclusion of LNA bases in antisense ONs augments the interference of HIV-1 genome dimerization. We also demonstrate the concomitant RNase H activation by six consecutive DNA bases in an LNA/DNA mix-mer. We show ON uptake via receptor-mediated transfection of a human T-cell line in which the mix-mers subsequently inhibit replication of a clinical HIV-1 isolate. Thus, the technique of LNA/DNA mix-mer antisense ONs targeting the conserved HIV-1 DIS region may provide a strategy to prevent HIV-1 assembly in the clinic. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：285 / 290

页数：6

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