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

Joacim Elmén, Hong Yan Zhang, Bartek Zuber, Karl Ljungberg, Britta Wahren, Claes R Wahlestedt, Zicai Liang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalFEBS Letters
Volume578
Issue number3
DOIs
StatePublished - Dec 17 2004
Externally publishedYes

Fingerprint

Dimerization
Antisense Oligonucleotides
Virus Replication
Viruses
HIV-1
Genes
Genome
DNA
Oligonucleotides
Ribonuclease H
T-cells
Transfection
Toxicity
Nucleotides
Chemical activation
locked nucleic acid
T-Lymphocytes
Cell Line

Keywords

  • Antisense
  • Dimerization initiation site
  • HIV
  • LNA
  • RNase H

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication. / Elmén, Joacim; Zhang, Hong Yan; Zuber, Bartek; Ljungberg, Karl; Wahren, Britta; Wahlestedt, Claes R; Liang, Zicai.

In: FEBS Letters, Vol. 578, No. 3, 17.12.2004, p. 285-290.

Research output: Contribution to journalArticle

Elmén, Joacim ; Zhang, Hong Yan ; Zuber, Bartek ; Ljungberg, Karl ; Wahren, Britta ; Wahlestedt, Claes R ; Liang, Zicai. / Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication. In: FEBS Letters. 2004 ; Vol. 578, No. 3. pp. 285-290.
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