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 language | English (US) |
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Pages (from-to) | 285-290 |
Number of pages | 6 |
Journal | FEBS letters |
Volume | 578 |
Issue number | 3 |
DOIs | |
State | Published - Dec 17 2004 |
Externally published | Yes |
Keywords
- Antisense
- Dimerization initiation site
- HIV
- LNA
- RNase H
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology