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Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus

Identifieur interne : 000215 ( Istex/Corpus ); précédent : 000214; suivant : 000216

Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus

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

Source :

RBID : ISTEX:5107325DD02376C0857BDB142DAAD066D2A94220

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

Links to Exploration step

ISTEX:5107325DD02376C0857BDB142DAAD066D2A94220

Le document en format XML

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