Anti‐HIV Activity of Steric Block Oligonucleotides
Identifieur interne : 000783 ( Istex/Corpus ); précédent : 000782; suivant : 000784Anti‐HIV Activity of Steric Block Oligonucleotides
Auteurs : Gabriela Ivanova ; Andrey A. Arzumanov ; John J. Turner ; Sandrine Reigadas ; Jean-Jacques Toulmé ; Douglas E. Brown ; Andrew M. L. Lever ; Michael J. GaitSource :
- 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
Links to Exploration step
ISTEX:CAFFDAF94B73340C3DA4A2D41544C7990824BC20Le document en format XML
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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><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>oligonucleotides</json:string><json:string>oligonucleotide</json:string><json:string>steric</json:string><json:string>antisense</json:string><json:string>sirna</json:string><json:string>analog</json:string><json:string>nucleic acids</json:string><json:string>steric block oligonucleotides</json:string><json:string>antiviral</json:string><json:string>viral</json:string><json:string>cationic</json:string><json:string>immunodeficiency</json:string><json:string>virucidal</json:string><json:string>human immunodeficiency virus type</json:string><json:string>york academy</json:string><json:string>hela</json:string><json:string>ivanova</json:string><json:string>aptamers</json:string><json:string>replication</json:string><json:string>peptide</json:string><json:string>antisense oligonucleotides</json:string><json:string>nucleic</json:string><json:string>cationic lipids</json:string><json:string>cellular uptake</json:string><json:string>transcription</json:string><json:string>secondary structure</json:string><json:string>leader sequence</json:string><json:string>oligonucleotide analogues</json:string><json:string>virucidal activity</json:string><json:string>steric block</json:string><json:string>oligonucleotide backbone</json:string><json:string>acid drug</json:string><json:string>cellular delivery</json:string><json:string>clinical trials</json:string><json:string>binding site</json:string><json:string>cellular activity</json:string><json:string>inhibition</json:string><json:string>molecular strategies</json:string><json:string>first snapshots</json:string><json:string>packaging signal</json:string><json:string>nucleic acid</json:string><json:string>intracellular activity</json:string><json:string>medical research council</json:string><json:string>gene expression</json:string><json:string>solid line</json:string><json:string>oligodeoxynucleotide phosphorothioate</json:string><json:string>oligonucleotide aptamers</json:string><json:string>molecular biology</json:string><json:string>viral replication</json:string><json:string>steric block oligonucleotide</json:string><json:string>hela cells</json:string><json:string>antiviral activity</json:string><json:string>viral packaging signal</json:string><json:string>newer oligonucleotide analogs</json:string><json:string>virucidal agents</json:string><json:string>primer binding site</json:string><json:string>nucleosides nucleotides</json:string><json:string>nucleotide</json:string><json:string>cellular</json:string></teeft></keywords><author><json:item><name>GABRIELA IVANOVA</name><affiliations><json:string>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</json:string></affiliations></json:item><json:item><name>ANDREY A. ARZUMANOV</name><affiliations><json:string>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</json:string></affiliations></json:item><json:item><name>JOHN J. TURNER</name><affiliations><json:string>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</json:string></affiliations></json:item><json:item><name>SANDRINE REIGADAS</name><affiliations><json:string>Institut Européen de Chimie et Biologie, 33607 PESSAC, France</json:string></affiliations></json:item><json:item><name>JEAN‐JACQUES TOULMÉ</name><affiliations><json:string>Institut Européen de Chimie et Biologie, 33607 PESSAC, France</json:string></affiliations></json:item><json:item><name>DOUGLAS E. BROWN</name><affiliations><json:string>Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK</json:string></affiliations></json:item><json:item><name>ANDREW M.L. 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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.</abstract><qualityIndicators><score>8.966</score><pdfWordCount>4698</pdfWordCount><pdfCharCount>29883</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>13</pdfPageCount><pdfPageSize>432 x 648 pts</pdfPageSize><pdfWordsPerPage>361</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>true</refBibsNative><abstractWordCount>189</abstractWordCount><abstractCharCount>1335</abstractCharCount><keywordCount>5</keywordCount></qualityIndicators><title>Anti‐HIV Activity of Steric Block Oligonucleotides</title><pmid><json:string>17145931</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Annals of the New York Academy of Sciences</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1749-6632</json:string></doi><issn><json:string>0077-8923</json:string></issn><eissn><json:string>1749-6632</json:string></eissn><publisherId><json:string>NYAS</json:string></publisherId><volume>1082</volume><issue>1</issue><pages><first>103</first><last>115</last><total>13</total></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1997</json:string><json:string>2006</json:string><json:string>2004</json:string></date><geogName></geogName><orgName><json:string>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB</json:string><json:string>UK ABSTRACT</json:string><json:string>University of Montpellier</json:string><json:string>Department of Medicine, University of Cambridge, Addenbrooke</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>B. 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<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><p><hi rend="bold"><hi rend="smallCaps">Abstract: </hi></hi>
<hi rend="bold">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 <hi rend="italic">trans</hi>‐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 <hi rend="italic">in vitro</hi> 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.</hi>
</p></abstract><textClass><keywords xml:lang="en"><term xml:id="k1">HIV</term><term xml:id="k2">antiviral</term><term xml:id="k3">virucide</term><term xml:id="k4">oligonucleotide</term><term xml:id="k5">steric block</term></keywords><keywords rend="tocHeading1"><term>Part II. Identifying and Validating Targets and Systems</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-3RJ6MB0K-B/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Inc</publisherName><publisherLoc>Malden, USA</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1749-6632</doi><issn type="print">0077-8923</issn><issn type="electronic">1749-6632</issn><idGroup><id type="product" value="NYAS"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="ANNALS OF NEW YORK ACADEMY SCIENCES">Annals of the New York Academy of Sciences</title></titleGroup></publicationMeta><publicationMeta level="part" position="10001"><doi origin="wiley">10.1111/nyas.2006.1082.issue-1</doi><titleGroup><title type="main">Oligonucleotide Therapeutics: First Annual Meeting of the Oligonucleotide Therapeutics Society</title></titleGroup><numberingGroup><numbering type="journalVolume" number="1082">1082</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2006-10">October 2006</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="15" status="forIssue"><doi origin="wiley">10.1196/annals.1348.033</doi><idGroup><id type="unit" value="NYAS33"></id></idGroup><countGroup><count type="pageTotal" number="13"></count></countGroup><titleGroup><title type="tocHeading1">Part II. Identifying and Validating Targets and Systems</title></titleGroup><eventGroup><event type="firstOnline" date="2006-11-17"></event><event type="publishedOnlineFinalForm" date="2006-11-17"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.5 mode:FullText source:FullText result:FullText" date="2010-04-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-19"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="103">103</numbering><numbering type="pageLast" number="115">115</numbering></numberingGroup><correspondenceTo>Address for correspondence: Michael J. Gait, Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK. Voice: +44‐1223‐248011; fax: +44‐1223‐402070.
e‐mail: <email normalForm="mgait@mrc-lmb.cam.ac.uk">mgait@mrc‐lmb.cam.ac.uk</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:NYAS.NYAS33.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="61"></count><count type="linksCrossRef" number="79"></count></countGroup><titleGroup><title type="main">Anti‐HIV Activity of Steric Block Oligonucleotides</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>GABRIELA</givenNames><familyName>IVANOVA</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>ANDREY A.</givenNames><familyName>ARZUMANOV</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>JOHN J.</givenNames><familyName>TURNER</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>SANDRINE</givenNames><familyName>REIGADAS</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a2"><personName><givenNames>JEAN‐JACQUES</givenNames><familyName>TOULMÉ</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a3"><personName><givenNames>DOUGLAS E.</givenNames><familyName>BROWN</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a3"><personName><givenNames>ANDREW M.L.</givenNames><familyName>LEVER</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a1"><personName><givenNames>MICHAEL J.</givenNames><familyName>GAIT</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="GB"><unparsedAffiliation>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="FR"><unparsedAffiliation>Institut Européen de Chimie et Biologie, 33607 PESSAC, France</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="GB"><unparsedAffiliation>Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">HIV</keyword><keyword xml:id="k2">antiviral</keyword><keyword xml:id="k3">virucide</keyword><keyword xml:id="k4">oligonucleotide</keyword><keyword xml:id="k5">steric block</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b><sc>Abstract: </sc></b> <b>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 <i>trans</i>‐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 <i>in vitro</i> 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.</b> </p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Anti‐HIV Activity of Steric Block Oligonucleotides</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Anti‐HIV Activity of Steric Block Oligonucleotides</title></titleInfo><name type="personal"><namePart type="given">GABRIELA</namePart><namePart type="family">IVANOVA</namePart><affiliation>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">ANDREY A.</namePart><namePart type="family">ARZUMANOV</namePart><affiliation>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JOHN J.</namePart><namePart type="family">TURNER</namePart><affiliation>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">SANDRINE</namePart><namePart type="family">REIGADAS</namePart><affiliation>Institut Européen de Chimie et Biologie, 33607 PESSAC, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JEAN‐JACQUES</namePart><namePart type="family">TOULMÉ</namePart><affiliation>Institut Européen de Chimie et Biologie, 33607 PESSAC, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">DOUGLAS E.</namePart><namePart type="family">BROWN</namePart><affiliation>Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">ANDREW M.L.</namePart><namePart type="family">LEVER</namePart><affiliation>Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">MICHAEL J.</namePart><namePart type="family">GAIT</namePart><affiliation>Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Blackwell Publishing Inc</publisher><place><placeTerm type="text">Malden, USA</placeTerm></place><dateIssued encoding="w3cdtf">2006-10</dateIssued><copyrightDate encoding="w3cdtf">2006</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">0</extent><extent unit="formulas">0</extent><extent unit="references">61</extent><extent unit="linksCrossRef">79</extent></physicalDescription><abstract 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.</abstract><subject lang="en"><genre>keywords</genre><topic>HIV</topic><topic>antiviral</topic><topic>virucide</topic><topic>oligonucleotide</topic><topic>steric block</topic></subject><relatedItem type="host"><titleInfo><title>Annals of the New York Academy of Sciences</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><identifier type="ISSN">0077-8923</identifier><identifier type="eISSN">1749-6632</identifier><identifier type="DOI">10.1111/(ISSN)1749-6632</identifier><identifier type="PublisherID">NYAS</identifier><part><date>2006</date><detail type="title"><title>Oligonucleotide Therapeutics: First Annual Meeting of the Oligonucleotide Therapeutics Society</title></detail><detail type="volume"><caption>vol.</caption><number>1082</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>103</start><end>115</end><total>13</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit1"><titleInfo><title>HIV‐chemotherapy and ‐prophylaxis: new drugs, leads and approaches</title></titleInfo><name type="personal"><namePart type="given">E.</namePart><namePart type="family">De Clercq</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">De Clercq, E. 2004. 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|texte= Anti‐HIV Activity of Steric Block Oligonucleotides
}}
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