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Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus

Identifieur interne : 004102 ( Main/Exploration ); précédent : 004101; suivant : 004103

Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus

Auteurs : Sang-Gug Kim [Japon] ; Toshifumi Hatta [Japon] ; Satoru Tsukahara [Japon] ; Hideki Nakashima [Japon] ; Naoki Yamamoto [Japon] ; Yoko Shoji [Japon] ; Kazuyuki Takai [Japon] ; Hiroshi Takaku [Japon]

Source :

RBID : ISTEX:5107325DD02376C0857BDB142DAAD066D2A94220

Descripteurs français

English descriptors

Abstract

Abstract: Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.

Url:
DOI: 10.1016/0968-0896(94)00142-P


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Antiviral Agents (chemical synthesis)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Base Sequence</term>
<term>Cell Line</term>
<term>DNA, Viral</term>
<term>Gene Targeting</term>
<term>HIV-1 (drug effects)</term>
<term>HIV-1 (physiology)</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
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<term>Oligonucleotides, Antisense (pharmacology)</term>
<term>Thionucleotides (chemical synthesis)</term>
<term>Thionucleotides (pharmacology)</term>
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<term>ADN viral</term>
<term>Antiviraux (pharmacologie)</term>
<term>Antiviraux (synthèse chimique)</term>
<term>Ciblage de gène</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Oligonucléotides antisens (pharmacologie)</term>
<term>Oligonucléotides antisens (synthèse chimique)</term>
<term>Réplication virale ()</term>
<term>Séquence nucléotidique</term>
<term>Thionucléotides (pharmacologie)</term>
<term>Thionucléotides (synthèse chimique)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term>
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<term>Antiviral Agents</term>
<term>Oligonucleotides, Antisense</term>
<term>Thionucleotides</term>
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<term>Antiviral Agents</term>
<term>Oligonucleotides, Antisense</term>
<term>Thionucleotides</term>
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<term>HIV-1</term>
<term>Virus Replication</term>
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<term>Antiviraux</term>
<term>Oligonucléotides antisens</term>
<term>Thionucléotides</term>
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<term>Antiviraux</term>
<term>Oligonucléotides antisens</term>
<term>Thionucléotides</term>
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<term>Acad</term>
<term>Acceptor</term>
<term>Antisense</term>
<term>Antisense oligomers</term>
<term>Antisense oligonucleotides</term>
<term>Antisense sequences</term>
<term>Antiviral effect</term>
<term>Base Sequence</term>
<term>Cell Line</term>
<term>Cellular uptake</term>
<term>Chain length</term>
<term>Chain lengths</term>
<term>Chiba institute</term>
<term>Culture medium</term>
<term>DNA, Viral</term>
<term>Different target sites</term>
<term>Gene Targeting</term>
<term>Human immunodeficiency virus</term>
<term>Humans</term>
<term>Inhibitory effect</term>
<term>Initiator codon</term>
<term>Molecular Sequence Data</term>
<term>Mrna processing</term>
<term>Nail acad</term>
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<term>Natl acad</term>
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<term>Oligomer</term>
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<term>Oligonucleotide</term>
<term>Oligonucleotides</term>
<term>Other hand</term>
<term>Particular interest</term>
<term>Phosphorothioate</term>
<term>Phosphorothioate group</term>
<term>Phosphorothioate groups</term>
<term>Phosphorothioate oligodeoxyribonucleotides</term>
<term>Phosphorothioate oligomer</term>
<term>Phosphorothioate oligomers</term>
<term>Phosphorothioate oligonucleotide analogues</term>
<term>Phosphorothioate oligonucleotides</term>
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<term>Random sequence</term>
<term>Replication</term>
<term>Sense sequence</term>
<term>Soodns oligomer</term>
<term>Splice</term>
<term>Splice acceptor</term>
<term>Splice acceptor sites</term>
<term>Target sequences</term>
<term>Target site</term>
<term>Test compounds</term>
<term>Viral</term>
<term>Viral expression</term>
<term>Viral replication</term>
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<term>Données de séquences moléculaires</term>
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<term>Lignée cellulaire</term>
<term>Réplication virale</term>
<term>Séquence nucléotidique</term>
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<div type="abstract" xml:lang="en">Abstract: Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.</div>
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