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

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article

26 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

Keywords

Antisense
Dimerization initiation site
HIV
LNA
RNase H

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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Elmén, J., Zhang, H. Y., Zuber, B., Ljungberg, K., Wahren, B., Wahlestedt, C., & Liang, Z. (2004). Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication. FEBS letters, 578(3), 285-290. https://doi.org/10.1016/j.febslet.2004.11.015

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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

AU - Ljungberg, Karl

AU - Wahren, Britta

AU - Wahlestedt, Claes

AU - Liang, Zicai

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KW - Antisense

KW - Dimerization initiation site

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KW - LNA

KW - RNase H

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