Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication.
Identifieur interne : 003052 ( Main/Exploration ); précédent : 003051; suivant : 003053Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV-1 genome dimerization and inhibit virus replication.
Auteurs : Joacim Elmén [Suède] ; Hong-Yan Zhang ; Bartek Zuber ; Karl Ljungberg ; Britta Wahren ; Claes Wahlestedt ; Zicai LiangSource :
- FEBS letters [ 0014-5793 ] ; 2004.
Descripteurs français
- KwdFr :
- Activation enzymatique, Cellules Jurkat, Dimérisation, Génome viral, Humains, Lymphocytes T (), Lymphocytes T (métabolisme), Oligonucléotides antisens (), Oligonucléotides antisens (pharmacologie), Ribonuclease H (métabolisme), Réplication virale (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (isolement et purification).
- MESH :
- génétique : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- isolement et purification : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : Lymphocytes T, Ribonuclease H.
- pharmacologie : Oligonucléotides antisens.
- Activation enzymatique, Cellules Jurkat, Dimérisation, Génome viral, Humains, Lymphocytes T, Oligonucléotides antisens, Réplication virale, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Dimerization, Enzyme Activation, Genome, Viral, HIV-1 (drug effects), HIV-1 (genetics), HIV-1 (isolation & purification), Humans, Jurkat Cells, Oligonucleotides, Antisense (chemistry), Oligonucleotides, Antisense (pharmacology), Ribonuclease H (metabolism), T-Lymphocytes (drug effects), T-Lymphocytes (metabolism), Virus Replication (drug effects).
- MESH :
- chemical , chemistry : Oligonucleotides, Antisense.
- drug effects : HIV-1, T-Lymphocytes, Virus Replication.
- genetics : HIV-1.
- isolation & purification : HIV-1.
- chemical , metabolism : Ribonuclease H, T-Lymphocytes.
- chemical , pharmacology : Oligonucleotides, Antisense.
- Dimerization, Enzyme Activation, Genome, Viral, Humans, Jurkat Cells.
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.
DOI: 10.1016/j.febslet.2004.11.015
PubMed: 15589834
Affiliations:
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Le document en format XML
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first="Joacim" last="Elmén">Joacim Elmén</name><affiliation wicri:level="1"><nlm:affiliation>Center for Genomics and Bioinformatics, Karolinska Institutet, Berzeliusväg 35, 171 77 Stockholm, Sweden. joacim.elmen@cgb.ki.se</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Center for Genomics and Bioinformatics, Karolinska Institutet, Berzeliusväg 35, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Hong Yan" sort="Zhang, Hong Yan" uniqKey="Zhang H" first="Hong-Yan" last="Zhang">Hong-Yan Zhang</name></author><author><name sortKey="Zuber, Bartek" sort="Zuber, Bartek" uniqKey="Zuber B" first="Bartek" last="Zuber">Bartek Zuber</name></author><author><name sortKey="Ljungberg, Karl" sort="Ljungberg, Karl" uniqKey="Ljungberg K" first="Karl" last="Ljungberg">Karl Ljungberg</name></author><author><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name></author><author><name sortKey="Wahlestedt, Claes" sort="Wahlestedt, Claes" uniqKey="Wahlestedt C" first="Claes" last="Wahlestedt">Claes Wahlestedt</name></author><author><name sortKey="Liang, Zicai" sort="Liang, Zicai" uniqKey="Liang Z" first="Zicai" last="Liang">Zicai Liang</name></author></analytic><series><title level="j">FEBS letters</title><idno type="ISSN">0014-5793</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dimerization</term><term>Enzyme Activation</term><term>Genome, Viral</term><term>HIV-1 (drug effects)</term><term>HIV-1 (genetics)</term><term>HIV-1 (isolation & purification)</term><term>Humans</term><term>Jurkat Cells</term><term>Oligonucleotides, Antisense (chemistry)</term><term>Oligonucleotides, Antisense (pharmacology)</term><term>Ribonuclease H (metabolism)</term><term>T-Lymphocytes (drug effects)</term><term>T-Lymphocytes (metabolism)</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique</term><term>Cellules Jurkat</term><term>Dimérisation</term><term>Génome viral</term><term>Humains</term><term>Lymphocytes T ()</term><term>Lymphocytes T (métabolisme)</term><term>Oligonucléotides antisens ()</term><term>Oligonucléotides antisens (pharmacologie)</term><term>Ribonuclease H (métabolisme)</term><term>Réplication virale ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique)</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (isolement et purification)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term><term>T-Lymphocytes</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Ribonuclease H</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lymphocytes T</term><term>Ribonuclease H</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dimerization</term><term>Enzyme Activation</term><term>Genome, Viral</term><term>Humans</term><term>Jurkat Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term><term>Cellules Jurkat</term><term>Dimérisation</term><term>Génome viral</term><term>Humains</term><term>Lymphocytes T</term><term>Oligonucléotides antisens</term><term>Réplication virale</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Suède</li></country></list><tree><noCountry><name sortKey="Liang, Zicai" sort="Liang, Zicai" uniqKey="Liang Z" first="Zicai" last="Liang">Zicai Liang</name><name sortKey="Ljungberg, Karl" sort="Ljungberg, Karl" uniqKey="Ljungberg K" first="Karl" last="Ljungberg">Karl Ljungberg</name><name sortKey="Wahlestedt, Claes" sort="Wahlestedt, Claes" uniqKey="Wahlestedt C" first="Claes" last="Wahlestedt">Claes Wahlestedt</name><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name><name sortKey="Zhang, Hong Yan" sort="Zhang, Hong Yan" uniqKey="Zhang H" first="Hong-Yan" last="Zhang">Hong-Yan Zhang</name><name sortKey="Zuber, Bartek" sort="Zuber, Bartek" uniqKey="Zuber B" first="Bartek" last="Zuber">Bartek Zuber</name></noCountry><country name="Suède"><noRegion><name sortKey="Elmen, Joacim" sort="Elmen, Joacim" uniqKey="Elmen J" first="Joacim" last="Elmén">Joacim Elmén</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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