Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes
Identifieur interne : 001E08 ( Istex/Corpus ); précédent : 001E07; suivant : 001E09Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes
Auteurs : Olivier Zelphati ; Ernst Wagner ; Lee LesermanSource :
- Antiviral Research [ 0166-3542 ] ; 1994.
English descriptors
- Teeft :
- Acad, Antisense, Antisense oligonucleotides, Antiviral, Antiviral activity, Antiviral effects, Antiviral research, Aqueous phase, Boutorine, Dnase, Encapsulated, Encapsulation, Filtration, Final concentration, Human immunodeficiency virus, Immunoliposomes, Intracellular delivery, Leserman, Lipid, Liposome, Machy, Monoclonal antibodies, Natl, Nuclease, Nucleic acids, Oberhauser, Oligodeoxynucleotides, Oligonucleotide, Oligonucleotides, Oligonucleotides encapsulated, Pharmacia, Phosphodiester, Phosphodiester oligonucleotides, Proc, Replication, Target cells, Target specificity, Total volume, Transport system, Unmodified, Unmodified oligonucleotides, Viral, Zelphati.
Abstract
Abstract: Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC50 around 0.1 μM). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.
Url:
DOI: 10.1016/0166-3542(94)90090-6
Links to Exploration step
ISTEX:402F4A53C455A4368088B79054268023BB9A14E8Le document en format XML
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This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC50 around 0.1 μM). 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Fax: + 33 91 26 94 30.</json:string><json:string>Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille, Luminy Case 906, 13288 Marseille Cedex 9, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>HIV-1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Oligonucleotide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Liposome</value></json:item></subject><arkIstex>ark:/67375/6H6-J9N8ZK0T-6</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC50 around 0.1 μM). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.</abstract><qualityIndicators><score>9.4</score><pdfWordCount>5075</pdfWordCount><pdfCharCount>34049</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>13</pdfPageCount><pdfPageSize>504 x 663 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>200</abstractWordCount><abstractCharCount>1530</abstractCharCount><keywordCount>3</keywordCount></qualityIndicators><title>Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes</title><pmid><json:string>7811058</json:string></pmid><pii><json:string>0166-3542(94)90090-6</json:string></pii><genre><json:string>research-article</json:string></genre><serie><title>Proc. Natl. Acad. Sci. USA</title><language><json:string>unknown</json:string></language><volume>85</volume><pages><first>5507</first><last>5511</last></pages></serie><host><title>Antiviral Research</title><language><json:string>unknown</json:string></language><publicationDate>1994</publicationDate><issn><json:string>0166-3542</json:string></issn><pii><json:string>S0166-3542(00)X0185-4</json:string></pii><volume>25</volume><issue>1</issue><pages><first>13</first><last>25</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1994</json:string></date><geogName></geogName><orgName><json:string>Genset</json:string><json:string>Aalto Bioreagents, Dublin</json:string><json:string>Institute of Molecular Pathology</json:string><json:string>Austria Received</json:string><json:string>Austrian Industrial Research Promotion Fund</json:string><json:string>American Type Culture Collection, Rockville, MD, USA</json:string><json:string>Ligue National Fran</json:string><json:string>ANRS</json:string><json:string>Centre National</json:string></orgName><orgName_funder><json:string>Ligue National Fran</json:string><json:string>ANRS</json:string><json:string>Centre National</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Bohr Gasse</json:string><json:string>O. Zelphatiet</json:string><json:string>L. Montagnier</json:string><json:string>Quentin Sattentau</json:string><json:string>Karl Mechtler</json:string></persName><placeName><json:string>Birmingham</json:string><json:string>Paris</json:string><json:string>Eppendorf</json:string><json:string>Canada</json:string><json:string>Vancouver</json:string><json:string>USA</json:string><json:string>Vienna</json:string><json:string>Denmark</json:string><json:string>AL</json:string><json:string>France</json:string><json:string>Roskilde</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Matthay et al., 1989</json:string><json:string>Shea et al., 1990</json:string><json:string>O. Zelphati et al.</json:string><json:string>Boutorine et al., 1993</json:string><json:string>Feener et al., 1990</json:string><json:string>Svinarchuk et al., 1993</json:string><json:string>Thierry et al., 1992</json:string><json:string>Leserman et al., 1980</json:string><json:string>Loke et al., 1989</json:string><json:string>Saison-Behmoaras et al., 1991</json:string><json:string>Zamecnik et al., 1986</json:string><json:string>Kim et al., 1991</json:string><json:string>Machy et al., 1990</json:string><json:string>Boutorine et al., 1992</json:string><json:string>Akhtar et al., 1991</json:string><json:string>Goodchild et al., 1988</json:string><json:string>Leserman et al., 1990</json:string><json:string>Shaw et al., 1991</json:string><json:string>Crooke et al., 1993</json:string><json:string>de Smidt et al., 1991</json:string><json:string>Machy et al., 1983</json:string><json:string>Stein et al., 1991</json:string><json:string>Lemke et al., 1979</json:string><json:string>Oberhauser and Wagner, 1992</json:string><json:string>Leonetti et al., 1990</json:string><json:string>Hope et al., 1985</json:string><json:string>Boutorine et al., 1990</json:string><json:string>Rey et al., 1984</json:string><json:string>Machy et al., 1982</json:string><json:string>Letsinger et al., 1989</json:string><json:string>Krieg et al., 1993</json:string><json:string>Gamper et al., 1993</json:string><json:string>Boutorine et al., 1989</json:string><json:string>Kinchington et al., 1992</json:string><json:string>Zelphati et al., 1993</json:string><json:string>Uhlmann et al., 1990</json:string><json:string>Matsukura et al., 1987</json:string><json:string>Yakubov et al., 1989</json:string><json:string>Kabanov et al., 1990</json:string><json:string>Senior, 1987</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-J9N8ZK0T-6</json:string></ark><categories><wos><json:string>1 - 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Fax: + 33 91 26 94 30.</affiliation><affiliation>Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille, Luminy Case 906, 13288 Marseille Cedex 9, France</affiliation></author><idno type="istex">402F4A53C455A4368088B79054268023BB9A14E8</idno><idno type="ark">ark:/67375/6H6-J9N8ZK0T-6</idno><idno type="DOI">10.1016/0166-3542(94)90090-6</idno><idno type="PII">0166-3542(94)90090-6</idno></analytic><monogr><title level="j">Antiviral Research</title><title level="j" type="abbrev">AVR</title><idno type="pISSN">0166-3542</idno><idno type="PII">S0166-3542(00)X0185-4</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994"></date><biblScope unit="volume">25</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="13">13</biblScope><biblScope unit="page" to="25">25</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC50 around 0.1 μM). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>HIV-1</term></item><item><term>Oligonucleotide</term></item><item><term>Liposome</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1994">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-J9N8ZK0T-6/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>AVR</jid><aid>94900906</aid><ce:pii>0166-3542(94)90090-6</ce:pii><ce:doi>10.1016/0166-3542(94)90090-6</ce:doi><ce:copyright type="unknown" year="1994"></ce:copyright></item-info><head><ce:dochead><ce:textfn>Research article</ce:textfn></ce:dochead><ce:title>Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes</ce:title><ce:author-group><ce:author><ce:given-name>Olivier</ce:given-name><ce:surname>Zelphati</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Ernst</ce:given-name><ce:surname>Wagner</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Lee</ce:given-name><ce:surname>Leserman</ce:surname><ce:cross-ref refid="COR1"><ce:sup>∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille, Luminy Case 906, 13288 Marseille Cedex 9, France</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Institute of Molecular Pathology, Dr. Bohr Gasse 7, A-1030 Vienna, Austria</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>∗</ce:label><ce:text>Corresponding author. Fax: + 33 91 26 94 30.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="12" month="2" year="1994"></ce:date-received><ce:date-accepted day="24" month="3" year="1994"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the <ce:italic>tat</ce:italic> gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC<ce:inf>50</ce:inf> around 0.1 μM). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>HIV-1</ce:text></ce:keyword><ce:keyword><ce:text>Oligonucleotide</ce:text></ce:keyword><ce:keyword><ce:text>Liposome</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes</title></titleInfo><name type="personal"><namePart type="given">Olivier</namePart><namePart type="family">Zelphati</namePart><affiliation>Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille, Luminy Case 906, 13288 Marseille Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ernst</namePart><namePart type="family">Wagner</namePart><affiliation>Institute of Molecular Pathology, Dr. Bohr Gasse 7, A-1030 Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lee</namePart><namePart type="family">Leserman</namePart><affiliation>Corresponding author. Fax: + 33 91 26 94 30.</affiliation><affiliation>Centre d'Immunologie, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille, Luminy Case 906, 13288 Marseille Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued><copyrightDate encoding="w3cdtf">1994</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (EC50 around 0.1 μM). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.</abstract><note type="content">Section title: Research article</note><subject><genre>Keywords</genre><topic>HIV-1</topic><topic>Oligonucleotide</topic><topic>Liposome</topic></subject><relatedItem type="host"><titleInfo><title>Antiviral Research</title></titleInfo><titleInfo type="abbreviated"><title>AVR</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued></originInfo><identifier type="ISSN">0166-3542</identifier><identifier type="PII">S0166-3542(00)X0185-4</identifier><part><date>1994</date><detail type="volume"><number>25</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1</start><end>80</end></extent><extent unit="pages"><start>13</start><end>25</end></extent></part></relatedItem><identifier type="istex">402F4A53C455A4368088B79054268023BB9A14E8</identifier><identifier type="ark">ark:/67375/6H6-J9N8ZK0T-6</identifier><identifier type="DOI">10.1016/0166-3542(94)90090-6</identifier><identifier type="PII">0166-3542(94)90090-6</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-J9N8ZK0T-6/record.json</uri></json:item></metadata></istex></record>Pour manipuler ce document sous Unix (Dilib)
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