Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV‐1 genome dimerization and inhibit virus replication
- 20 November 2004
- journal article
- Published by Wiley in FEBS Letters
- Vol. 578 (3) , 285-290
- https://doi.org/10.1016/j.febslet.2004.11.015
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.Keywords
This publication has 43 references indexed in Scilit:
- Dimerization of retroviral RNA genomes: an inseparable pairNature Reviews Microbiology, 2004
- Nucleic-acid therapeutics: basic principles and recent applicationsNature Reviews Drug Discovery, 2002
- Antisense and sensibilityNature Biotechnology, 2002
- Inhibition of HIV-1 Tat-Dependent Trans Activation by Steric Block Chimeric 2‘-O-Methyl/LNA OligoribonucleotidesBiochemistry, 2001
- OLIGONUCLEOTIDE ANALOGUE INTERFERENCE WITH THE HIV-1 TAT PROTEIN-TAR RNA INTERACTIONNucleosides, Nucleotides and Nucleic Acids, 2001
- LNA (Locked Nucleic Acid): An RNA Mimic Forming Exceedingly Stable LNA:LNA DuplexesJournal of the American Chemical Society, 1998
- Oligonucleotide-Mediated Inhibition of Genomic RNA Dimerization of HIV-1 Strains MAL and LAI: A Comparative AnalysisAntisense and Nucleic Acid Drug Development, 1998
- LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognitionChemical Communications, 1998
- Coupling of cell-binding ligands to polyethylenimine for targeted gene deliveryGene Therapy, 1997
- Mechanisms of Inhibition of in Vitro Dimerization of HIV Type I RNA by Sense and Antisense OligonucleotidesJournal of Biological Chemistry, 1996