About: 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.   Goto Sponge  NotDistinct  Permalink

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  • 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.
subject
  • Virology
  • DNA
  • Nucleic acids
  • HIV/AIDS
  • Causes of death
  • Membrane biology
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