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Antisense oligonucleotides: gene regulation and chemotherapy of AIDS

Identifieur interne : 000398 ( Istex/Corpus ); précédent : 000397; suivant : 000399

Antisense oligonucleotides: gene regulation and chemotherapy of AIDS

Auteurs : Sudhir Agrawal ; Prem S. Sarin

Source :

RBID : ISTEX:50A1BA6B6CFCE21A80880ECCEB083AC5D2C8CFC8

English descriptors

Abstract

Abstract: The use of antisense oligonucleotides in control of gene regulation and inhibition of virus replication is a unique approach designed to interfere with cell and virus replication, transcription and translation machinery at the molecular level. Extensive studies ave been carried out to regulate replication of human immunodeficiency virus by synthetic oligonucleotides and their several sugar phosphate backbone modified analogues. Thus far, studies have been carried out in tissue culture, and inhibition of HIV expression has been monitored by several parameters. Oligonucleotide phosphorothioates are effective in inhibiting HIV expression in tissue culture at a concentration of 1·10−7 M, which translates into a dose of approximately 0.6 mg/kg bodyweight. A non-toxic dose of 100 mg/kg, in preliminary acute toxicity experiments, represents an exploitable therapeutic window for ‘oligonucleotide therapy’.

Url:
DOI: 10.1016/0169-409X(91)90020-D

Links to Exploration step

ISTEX:50A1BA6B6CFCE21A80880ECCEB083AC5D2C8CFC8

Le document en format XML

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<ce:title>Antisense oligonucleotides: gene regulation and chemotherapy of AIDS</ce:title>
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<ce:given-name>Sudhir</ce:given-name>
<ce:surname>Agrawal</ce:surname>
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<ce:given-name>Prem S.</ce:given-name>
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<ce:text>Correspondence: S. Agrawal, Worcester Foundation for Experimental Biology, 222 Maple Avenue, Shrewsbury, MA 01545, U.S.A.</ce:text>
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<ce:simple-para>The use of antisense oligonucleotides in control of gene regulation and inhibition of virus replication is a unique approach designed to interfere with cell and virus replication, transcription and translation machinery at the molecular level. Extensive studies ave been carried out to regulate replication of human immunodeficiency virus by synthetic oligonucleotides and their several sugar phosphate backbone modified analogues. Thus far, studies have been carried out in tissue culture, and inhibition of HIV expression has been monitored by several parameters. Oligonucleotide phosphorothioates are effective in inhibiting HIV expression in tissue culture at a concentration of 1·10
<ce:sup>−7</ce:sup>
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<ce:text>Antisense oligonucleotide</ce:text>
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<ce:text>Human immunodeficiency virus</ce:text>
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<ce:keyword>
<ce:text>AZT, zidovudine</ce:text>
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<ce:keyword>
<ce:text>HIV, human immunodeficiency virus</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>nef or NEF, negative regulation factor</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>PBS, primer binding site</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>RIPA, radioimmunoprecipitation assay</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>TAR, transactivator responsive region</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>tRNA, transfer RNA</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>vif or VIF, viral infectivity factor</ce:text>
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<abstract lang="en">Abstract: The use of antisense oligonucleotides in control of gene regulation and inhibition of virus replication is a unique approach designed to interfere with cell and virus replication, transcription and translation machinery at the molecular level. Extensive studies ave been carried out to regulate replication of human immunodeficiency virus by synthetic oligonucleotides and their several sugar phosphate backbone modified analogues. Thus far, studies have been carried out in tissue culture, and inhibition of HIV expression has been monitored by several parameters. Oligonucleotide phosphorothioates are effective in inhibiting HIV expression in tissue culture at a concentration of 1·10−7 M, which translates into a dose of approximately 0.6 mg/kg bodyweight. A non-toxic dose of 100 mg/kg, in preliminary acute toxicity experiments, represents an exploitable therapeutic window for ‘oligonucleotide therapy’.</abstract>
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<topic>Chemotherapy of AIDS</topic>
<topic>Phosphorothioate</topic>
<topic>Methylphosphonate</topic>
<topic>Phosphoramidate</topic>
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<genre>Abbreviations</genre>
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<topic>AZT, zidovudine</topic>
<topic>DMF, dimethylformamide</topic>
<topic>Fmoc, 9-fluorenylmethoxycarbonyl</topic>
<topic>HIV, human immunodeficiency virus</topic>
<topic>nef or NEF, negative regulation factor</topic>
<topic>PBS, primer binding site</topic>
<topic>RIPA, radioimmunoprecipitation assay</topic>
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