Anti‐HIV Activity of Steric Block Oligonucleotides
Identifieur interne : 002E55 ( Main/Exploration ); précédent : 002E54; suivant : 002E56Anti‐HIV Activity of Steric Block Oligonucleotides
Auteurs : Gabriela Ivanova [Royaume-Uni] ; Andrey A. Arzumanov [Royaume-Uni] ; John J. Turner [Royaume-Uni] ; Sandrine Reigadas [France] ; Jean-Jacques Toulmé [France] ; Douglas E. Brown [Royaume-Uni] ; Andrew M. L. Lever [Royaume-Uni] ; Michael J. Gait [Royaume-Uni]Source :
- Annals of the New York Academy of Sciences [ 0077-8923 ] ; 2006-10.
English descriptors
- Teeft :
- Acid drug, Analog, Antisense, Antisense oligonucleotides, Antiviral, Antiviral activity, Aptamers, Binding site, Cationic, Cationic lipids, Cellular, Cellular activity, Cellular delivery, Cellular uptake, Clinical trials, First snapshots, Gene expression, Hela, Hela cells, Human immunodeficiency virus type, Immunodeficiency, Inhibition, Intracellular activity, Ivanova, Leader sequence, Medical research council, Molecular biology, Molecular strategies, Newer oligonucleotide analogs, Nucleic, Nucleic acid, Nucleic acids, Nucleosides nucleotides, Nucleotide, Oligodeoxynucleotide phosphorothioate, Oligonucleotide, Oligonucleotide analogues, Oligonucleotide aptamers, Oligonucleotide backbone, Oligonucleotides, Packaging signal, Peptide, Primer binding site, Replication, Secondary structure, Sirna, Solid line, Steric, Steric block, Steric block oligonucleotide, Steric block oligonucleotides, Transcription, Viral, Viral packaging signal, Viral replication, Virucidal, Virucidal activity, Virucidal agents, York academy.
Abstract
Abstract: The unabated increase in spread of HIV infection worldwide has redoubled efforts to discover novel antiviral and virucidal agents that might be starting points for clinical development. Oligonucleotides and their analogs targeted to form complementary duplexes with highly conserved regions of the HIV RNA have shown significant antiviral activity, but to date clinical studies have been dominated by RNase H‐inducing oligonucleotide analog phosphorothioates (GEM 91 and 92) that have specificity and efficacy limitations. However, they have proven the principle that oligonucleotides can be safe anti‐HIV drugs. Newer oligonucleotide analogs are now available, which act as strong steric block agents of HIV RNA function. We describe our ongoing studies targeting the HIV‐1 trans‐activation responsive region (TAR) and the viral packaging signal (psi) with steric block oligonucleotides of varying chemistry and demonstrate their great potential for steric blocking of viral protein interactions in vitro and in cells and describe the first antiviral studies. Peptide nucleic acids (PNA) disulfide linked to cell‐penetrating peptides (CPP) have been found to have particular promise for the lipid‐free direct delivery into cultured cells and are excellent candidates for their development as antiviral and virucidal agents.
Url:
DOI: 10.1196/annals.1348.033
Affiliations:
- France, Royaume-Uni
- Angleterre, Angleterre de l'Est, Aquitaine, Nouvelle-Aquitaine
- Cambridge, PESSAC
- Université de Cambridge
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Le document en format XML
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Gait</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH</wicri:regionArea><wicri:noRegion>Cambridge CB2 2QH</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Annals of the New York Academy of Sciences</title><title level="j" type="alt">ANNALS OF NEW YORK ACADEMY SCIENCES</title><idno type="ISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><imprint><biblScope unit="vol">1082</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="103">103</biblScope><biblScope unit="page" to="115">115</biblScope><biblScope unit="page-count">13</biblScope><publisher>Blackwell Publishing Inc</publisher><pubPlace>Malden, USA</pubPlace><date type="published" when="2006-10">2006-10</date></imprint><idno type="ISSN">0077-8923</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0077-8923</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acid drug</term><term>Analog</term><term>Antisense</term><term>Antisense oligonucleotides</term><term>Antiviral</term><term>Antiviral activity</term><term>Aptamers</term><term>Binding site</term><term>Cationic</term><term>Cationic lipids</term><term>Cellular</term><term>Cellular activity</term><term>Cellular delivery</term><term>Cellular uptake</term><term>Clinical trials</term><term>First snapshots</term><term>Gene expression</term><term>Hela</term><term>Hela cells</term><term>Human immunodeficiency virus type</term><term>Immunodeficiency</term><term>Inhibition</term><term>Intracellular activity</term><term>Ivanova</term><term>Leader sequence</term><term>Medical research council</term><term>Molecular biology</term><term>Molecular strategies</term><term>Newer oligonucleotide analogs</term><term>Nucleic</term><term>Nucleic acid</term><term>Nucleic acids</term><term>Nucleosides nucleotides</term><term>Nucleotide</term><term>Oligodeoxynucleotide phosphorothioate</term><term>Oligonucleotide</term><term>Oligonucleotide analogues</term><term>Oligonucleotide aptamers</term><term>Oligonucleotide backbone</term><term>Oligonucleotides</term><term>Packaging signal</term><term>Peptide</term><term>Primer binding site</term><term>Replication</term><term>Secondary structure</term><term>Sirna</term><term>Solid line</term><term>Steric</term><term>Steric block</term><term>Steric block oligonucleotide</term><term>Steric block oligonucleotides</term><term>Transcription</term><term>Viral</term><term>Viral packaging signal</term><term>Viral replication</term><term>Virucidal</term><term>Virucidal activity</term><term>Virucidal agents</term><term>York academy</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The unabated increase in spread of HIV infection worldwide has redoubled efforts to discover novel antiviral and virucidal agents that might be starting points for clinical development. Oligonucleotides and their analogs targeted to form complementary duplexes with highly conserved regions of the HIV RNA have shown significant antiviral activity, but to date clinical studies have been dominated by RNase H‐inducing oligonucleotide analog phosphorothioates (GEM 91 and 92) that have specificity and efficacy limitations. However, they have proven the principle that oligonucleotides can be safe anti‐HIV drugs. Newer oligonucleotide analogs are now available, which act as strong steric block agents of HIV RNA function. We describe our ongoing studies targeting the HIV‐1 trans‐activation responsive region (TAR) and the viral packaging signal (psi) with steric block oligonucleotides of varying chemistry and demonstrate their great potential for steric blocking of viral protein interactions in vitro and in cells and describe the first antiviral studies. Peptide nucleic acids (PNA) disulfide linked to cell‐penetrating peptides (CPP) have been found to have particular promise for the lipid‐free direct delivery into cultured cells and are excellent candidates for their development as antiviral and virucidal agents.</div></front></TEI><affiliations><list><country><li>France</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Cambridge</li><li>PESSAC</li></settlement><orgName><li>Université de Cambridge</li></orgName></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Ivanova, Gabriela" sort="Ivanova, Gabriela" uniqKey="Ivanova G" first="Gabriela" last="Ivanova">Gabriela Ivanova</name></noRegion><name sortKey="Arzumanov, Andrey A" sort="Arzumanov, Andrey A" uniqKey="Arzumanov A" first="Andrey A." last="Arzumanov">Andrey A. Arzumanov</name><name sortKey="Brown, Douglas E" sort="Brown, Douglas E" uniqKey="Brown D" first="Douglas E." last="Brown">Douglas E. Brown</name><name sortKey="Gait, Michael J" sort="Gait, Michael J" uniqKey="Gait M" first="Michael J." last="Gait">Michael J. Gait</name><name sortKey="Lever, Andrew M L" sort="Lever, Andrew M L" uniqKey="Lever A" first="Andrew M. L." last="Lever">Andrew M. L. Lever</name><name sortKey="Turner, John J" sort="Turner, John J" uniqKey="Turner J" first="John J." last="Turner">John J. Turner</name></country><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Reigadas, Sandrine" sort="Reigadas, Sandrine" uniqKey="Reigadas S" first="Sandrine" last="Reigadas">Sandrine Reigadas</name></region><name sortKey="Toulme, Jean Acques" sort="Toulme, Jean Acques" uniqKey="Toulme J" first="Jean-Jacques" last="Toulmé">Jean-Jacques Toulmé</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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