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 Wahlestedt, Zicai Liang

Research output: Contribution to journalArticle

26 Scopus citations

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 (US)
Pages (from-to)285-290
Number of pages6
JournalFEBS letters
Volume578
Issue number3
DOIs
StatePublished - Dec 17 2004

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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