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 |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication
AU - Elmén, Joacim
AU - Zhang, Hong Yan
AU - Zuber, Bartek
AU - Ljungberg, Karl
AU - Wahren, Britta
AU - Wahlestedt, Claes R
AU - Liang, Zicai
PY - 2004/12/17
Y1 - 2004/12/17
N2 - 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.
AB - 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.
KW - Antisense
KW - Dimerization initiation site
KW - HIV
KW - LNA
KW - RNase H
UR - http://www.scopus.com/inward/record.url?scp=10044234020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10044234020&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2004.11.015
DO - 10.1016/j.febslet.2004.11.015
M3 - Article
C2 - 15589834
AN - SCOPUS:10044234020
VL - 578
SP - 285
EP - 290
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 3
ER -