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

doi:10.1016/j.febslet.2004.11.015

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 journal › Article › peer-review

27 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 language	English (US)
Pages (from-to)	285-290
Number of pages	6
Journal	FEBS letters
Volume	578
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2004.11.015
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

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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; Liang, Zicai.

In: FEBS letters, Vol. 578, No. 3, 17.12.2004, p. 285-290.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Elmén, Joacim

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AU - Zuber, Bartek

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AU - Wahren, Britta

AU - Wahlestedt, Claes

AU - Liang, Zicai

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