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

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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10.1016/j.febslet.2004.11.015

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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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title = "Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication",

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.",

keywords = "Antisense, Dimerization initiation site, HIV, LNA, RNase H",

author = "Joacim Elm{\'e}n and Zhang, {Hong Yan} and Bartek Zuber and Karl Ljungberg and Britta Wahren and Claes Wahlestedt and Zicai Liang",

note = "Funding Information: This work was supported by the PhD Program in Biotechnology with an Industrial Focus at Karolinska Institutet and Pharmacia Corporation. Plasmids for an initial study were kindly provided by Roland Marquet and Jean-Christophe Paillart (IBMC, Strasbourg, France). We thank Kajsa Aperia for viral stocks, Karin Mattsson for microscopy and Ola Larsson for statistical analysis.",

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AU - Elmén, Joacim

AU - Zhang, Hong Yan

AU - Zuber, Bartek

AU - Ljungberg, Karl

AU - Wahren, Britta

AU - Wahlestedt, Claes

AU - Liang, Zicai

N1 - Funding Information: This work was supported by the PhD Program in Biotechnology with an Industrial Focus at Karolinska Institutet and Pharmacia Corporation. Plasmids for an initial study were kindly provided by Roland Marquet and Jean-Christophe Paillart (IBMC, Strasbourg, France). We thank Kajsa Aperia for viral stocks, Karin Mattsson for microscopy and Ola Larsson for statistical analysis.

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

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Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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