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Antisense oligonucleotides: gene regulation and chemotherapy of AIDS

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

Antisense oligonucleotides: gene regulation and chemotherapy of AIDS

Auteurs : Sudhir Agrawal [États-Unis] ; Prem S. Sarin [États-Unis]

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

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ISTEX:50A1BA6B6CFCE21A80880ECCEB083AC5D2C8CFC8

Le document en format XML

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<term>Acad</term>
<term>Acceptor</term>
<term>Agrawal</term>
<term>Analogue</term>
<term>Antisense</term>
<term>Antisense oligomers</term>
<term>Antisense oligonucleotides</term>
<term>Antisense sequence</term>
<term>Assay</term>
<term>Biochemistry</term>
<term>Body weight</term>
<term>Cell culture</term>
<term>Chem</term>
<term>Chemotherapy</term>
<term>Cholesterol residue</term>
<term>Cytopathic</term>
<term>Cytopathic effect</term>
<term>Duplex</term>
<term>Gene regulation</term>
<term>Gene regulationand chemotherapyof aids</term>
<term>Higher concentration</term>
<term>Human immunodeficiency virus</term>
<term>Ids0</term>
<term>Inhibition</term>
<term>Internucleotide linkage</term>
<term>Lett</term>
<term>Linkage</term>
<term>Methylphospho</term>
<term>Methylphosphonate</term>
<term>Methylphosphonate linkage</term>
<term>Methylphosphonate linkages</term>
<term>Mrna</term>
<term>Natl</term>
<term>Nuclease</term>
<term>Nucleic</term>
<term>Nucleic acids</term>
<term>Oligodeoxynucleotide</term>
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<term>Oligomers</term>
<term>Oligonucleotide</term>
<term>Oligonucleotide methylphospho triester</term>
<term>Oligonucleotide phosphorothioates</term>
<term>Oligonucleotides</term>
<term>Phosphoroselenoate</term>
<term>Phosphorothioate</term>
<term>Phosphorothioate analogue</term>
<term>Phosphorothioate oligomer</term>
<term>Phosphorothioate oligomers</term>
<term>Proc</term>
<term>Protein synthesis</term>
<term>Replication</term>
<term>Sarin</term>
<term>Similar results</term>
<term>Splice</term>
<term>Splice acceptor site</term>
<term>Splice donor site</term>
<term>Syncytia formation</term>
<term>Syncytium</term>
<term>Tissue culture</term>
<term>Toxicity</term>
<term>Transcriptase</term>
<term>Transcriptase assay</term>
<term>Transcription</term>
<term>Triester</term>
<term>Trna</term>
<term>Unmodified</term>
<term>Unmodified oligomer</term>
<term>Unmodified oligonucleotide</term>
<term>Unmodified oligonucleotides</term>
<term>Viral</term>
<term>Virus replication</term>
<term>Zamecnik</term>
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<div type="abstract" xml: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’.</div>
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