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Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV‐1 genome dimerization and inhibit virus replication
Author(s) -
Elmén Joacim,
Zhang Hong-Yan,
Zuber Bartek,
Ljungberg Karl,
Wahren Britta,
Wahlestedt Claes,
Liang Zicai
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.015
Subject(s) - oligonucleotide , nucleic acid , genome , virology , chemistry , human immunodeficiency virus (hiv) , viral replication , replication (statistics) , biology , virus , dna , microbiology and biotechnology , biochemistry , gene
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.