Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery
Identifieur interne : 000E86 ( Istex/Corpus ); précédent : 000E85; suivant : 000E87Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery
Auteurs : Sergey Zaitsev ; Régis Cartier ; Oleg Vyborov ; Gleb Sukhorukov ; Bernd-Reiner Paulke ; Annekathrin Haberland ; Yelena Parfyonova ; Vsevolod Tkachuk ; Michael BöttgerSource :
- Pharmaceutical Research [ 0724-8741 ] ; 2004-09-01.
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Abstract
Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.
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DOI: 10.1023/B:PHAM.0000041462.19131.08
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Germany</mods:affiliation></affiliation></author><author><name sortKey="Vyborov, Oleg" sort="Vyborov, Oleg" uniqKey="Vyborov O" first="Oleg" last="Vyborov">Oleg Vyborov</name><affiliation><mods:affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</mods:affiliation></affiliation></author><author><name sortKey="Sukhorukov, Gleb" sort="Sukhorukov, Gleb" uniqKey="Sukhorukov G" first="Gleb" last="Sukhorukov">Gleb Sukhorukov</name><affiliation><mods:affiliation>Max Planck Institute of Colloids and Surfaces, D-14476, Golm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Paulke, Bernd Reiner" sort="Paulke, Bernd Reiner" uniqKey="Paulke B" first="Bernd-Reiner" last="Paulke">Bernd-Reiner Paulke</name><affiliation><mods:affiliation>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP), D-14476, Golm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Haberland, Annekathrin" sort="Haberland, 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last="Zaitsev">Sergey Zaitsev</name><affiliation><mods:affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</mods:affiliation></affiliation></author><author><name sortKey="Cartier, Regis" sort="Cartier, Regis" uniqKey="Cartier R" first="Régis" last="Cartier">Régis Cartier</name><affiliation><mods:affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</mods:affiliation></affiliation></author><author><name sortKey="Vyborov, Oleg" sort="Vyborov, Oleg" uniqKey="Vyborov O" first="Oleg" last="Vyborov">Oleg Vyborov</name><affiliation><mods:affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</mods:affiliation></affiliation></author><author><name sortKey="Sukhorukov, Gleb" sort="Sukhorukov, Gleb" uniqKey="Sukhorukov G" first="Gleb" last="Sukhorukov">Gleb Sukhorukov</name><affiliation><mods:affiliation>Max Planck Institute of Colloids and Surfaces, D-14476, Golm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Paulke, Bernd Reiner" sort="Paulke, Bernd Reiner" uniqKey="Paulke B" first="Bernd-Reiner" last="Paulke">Bernd-Reiner Paulke</name><affiliation><mods:affiliation>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP), D-14476, Golm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Haberland, Annekathrin" sort="Haberland, Annekathrin" uniqKey="Haberland A" first="Annekathrin" last="Haberland">Annekathrin Haberland</name><affiliation><mods:affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</mods:affiliation></affiliation></author><author><name sortKey="Parfyonova, Yelena" sort="Parfyonova, Yelena" uniqKey="Parfyonova Y" first="Yelena" last="Parfyonova">Yelena Parfyonova</name><affiliation><mods:affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</mods:affiliation></affiliation></author><author><name sortKey="Tkachuk, Vsevolod" sort="Tkachuk, Vsevolod" uniqKey="Tkachuk V" first="Vsevolod" last="Tkachuk">Vsevolod Tkachuk</name><affiliation><mods:affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</mods:affiliation></affiliation></author><author><name sortKey="Bottger, Michael" sort="Bottger, Michael" uniqKey="Bottger M" first="Michael" last="Böttger">Michael Böttger</name><affiliation><mods:affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><publisher>Kluwer Academic Publishers-Plenum Publishers</publisher><pubPlace>New York</pubPlace><date type="published" when="2004-09-01">2004-09-01</date><biblScope unit="volume">21</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1656">1656</biblScope><biblScope unit="page" to="1661">1661</biblScope></imprint><idno type="ISSN">0724-8741</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0724-8741</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>human urokinase plasminogen activator</term><term>nanoparticle-mediated gene 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The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Sergey Zaitsev</name><affiliations><json:string>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</json:string><json:string>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</json:string></affiliations></json:item><json:item><name>Régis Cartier</name><affiliations><json:string>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</json:string></affiliations></json:item><json:item><name>Oleg Vyborov</name><affiliations><json:string>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</json:string></affiliations></json:item><json:item><name>Gleb Sukhorukov</name><affiliations><json:string>Max Planck Institute of Colloids and Surfaces, D-14476, Golm, Germany</json:string></affiliations></json:item><json:item><name>Bernd-Reiner Paulke</name><affiliations><json:string>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP), D-14476, Golm, Germany</json:string></affiliations></json:item><json:item><name>Annekathrin Haberland</name><affiliations><json:string>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</json:string></affiliations></json:item><json:item><name>Yelena Parfyonova</name><affiliations><json:string>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</json:string></affiliations></json:item><json:item><name>Vsevolod Tkachuk</name><affiliations><json:string>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</json:string></affiliations></json:item><json:item><name>Michael Böttger</name><affiliations><json:string>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>β-gal expression</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>human urokinase plasminogen activator</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>nanoparticle-mediated gene transfer</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>vascular gene transfer</value></json:item></subject><articleId><json:string>492480</json:string><json:string>Art20</json:string></articleId><arkIstex>ark:/67375/VQC-12XTRJBH-N</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. 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D-13125, Berlin-Buch, Germany</affiliation><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Régis</forename><surname>Cartier</surname></persName><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Oleg</forename><surname>Vyborov</surname></persName><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Gleb</forename><surname>Sukhorukov</surname></persName><affiliation>Max Planck Institute of Colloids and Surfaces, D-14476, Golm, Germany</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Bernd-Reiner</forename><surname>Paulke</surname></persName><affiliation>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP), D-14476, Golm, Germany</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Annekathrin</forename><surname>Haberland</surname></persName><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Yelena</forename><surname>Parfyonova</surname></persName><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Vsevolod</forename><surname>Tkachuk</surname></persName><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Michael</forename><surname>Böttger</surname></persName><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation></author><idno type="istex">122722A2D7887D9C17FB2589D4276052190E49C3</idno><idno type="ark">ark:/67375/VQC-12XTRJBH-N</idno><idno type="DOI">10.1023/B:PHAM.0000041462.19131.08</idno><idno type="article-id">492480</idno><idno type="article-id">Art20</idno></analytic><monogr><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="pISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><idno type="journal-ID">true</idno><idno type="issue-article-count">30</idno><idno type="volume-issue-count">12</idno><imprint><publisher>Kluwer Academic Publishers-Plenum Publishers</publisher><pubPlace>New York</pubPlace><date type="published" when="2004-09-01"></date><biblScope unit="volume">21</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1656">1656</biblScope><biblScope unit="page" to="1661">1661</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><item><term>β-gal expression</term></item><item><term>human urokinase plasminogen activator</term></item><item><term>nanoparticle-mediated gene transfer</term></item><item><term>vascular gene transfer</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Biomedicine</head><item><term>Pharmacology/Toxicology</term></item><item><term>Pharmacy</term></item><item><term>Biochemistry, general</term></item><item><term>Medical Law</term></item><item><term>Biomedical Engineering</term></item></list></keywords></textClass></profileDesc><revisionDesc><change 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NumberingStyle="Unnumbered"><JournalID>11095</JournalID><JournalPrintISSN>0724-8741</JournalPrintISSN><JournalElectronicISSN>1573-904X</JournalElectronicISSN><JournalTitle>Pharmaceutical Research</JournalTitle><JournalSubTitle>An Official Journal of the American Association of Pharmaceutical Scientists</JournalSubTitle><JournalAbbreviatedTitle>Pharm Res</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Biomedicine</JournalSubject><JournalSubject Type="Secondary">Pharmacology/Toxicology</JournalSubject><JournalSubject Type="Secondary">Pharmacy</JournalSubject><JournalSubject Type="Secondary">Biochemistry, general</JournalSubject><JournalSubject Type="Secondary">Medical Law</JournalSubject><JournalSubject Type="Secondary">Biomedical Engineering</JournalSubject></JournalSubjectGroup></JournalInfo><Volume><VolumeInfo VolumeType="Regular" TocLevels="0"><VolumeIDStart>21</VolumeIDStart><VolumeIDEnd>21</VolumeIDEnd><VolumeIssueCount>12</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular"><IssueInfo TocLevels="0"><IssueIDStart>9</IssueIDStart><IssueIDEnd>9</IssueIDEnd><IssueArticleCount>30</IssueArticleCount><IssueHistory><CoverDate><Year>2004</Year><Month>9</Month></CoverDate></IssueHistory><IssueCopyright><CopyrightHolderName>Springer Science+Business Media, Inc.</CopyrightHolderName><CopyrightYear>2004</CopyrightYear></IssueCopyright></IssueInfo><Article ID="Art20"><ArticleInfo Language="En" ArticleType="OriginalPaper" NumberingStyle="Unnumbered" TocLevels="0" ContainsESM="No"><ArticleID>492480</ArticleID><ArticleDOI>10.1023/B:PHAM.0000041462.19131.08</ArticleDOI><ArticleSequenceNumber>20</ArticleSequenceNumber><ArticleTitle Language="En">Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery</ArticleTitle><ArticleFirstPage>1656</ArticleFirstPage><ArticleLastPage>1661</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2004</Year><Month>12</Month><Day>22</Day></RegistrationDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer Science+Business Media, Inc.</CopyrightHolderName><CopyrightYear>2004</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants><ArticleContext><JournalID>11095</JournalID><VolumeIDStart>21</VolumeIDStart><VolumeIDEnd>21</VolumeIDEnd><IssueIDStart>9</IssueIDStart><IssueIDEnd>9</IssueIDEnd></ArticleContext></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Sergey</GivenName><FamilyName>Zaitsev</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Régis</GivenName><FamilyName>Cartier</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Oleg</GivenName><FamilyName>Vyborov</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Gleb</GivenName><FamilyName>Sukhorukov</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff4"><AuthorName DisplayOrder="Western"><GivenName>Bernd-Reiner</GivenName><FamilyName>Paulke</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Annekathrin</GivenName><FamilyName>Haberland</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Yelena</GivenName><FamilyName>Parfyonova</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Vsevolod</GivenName><FamilyName>Tkachuk</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Michael</GivenName><FamilyName>Böttger</FamilyName></AuthorName></Author><Affiliation ID="Aff1"><OrgDivision>Franz Volhard Clinic</OrgDivision><OrgName>HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC)</OrgName><OrgAddress><Postcode>D-13125</Postcode><City>Berlin-Buch</City><Country>Germany</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgName>Institute of Cytology of the Russian Academy of Sciences</OrgName><OrgAddress><City>St. Petersburg</City><Postcode>194064</Postcode><Country>Russia</Country></OrgAddress></Affiliation><Affiliation ID="Aff3"><OrgName>Max Planck Institute of Colloids and Surfaces</OrgName><OrgAddress><Postcode>D-14476</Postcode><City>Golm</City><Country>Germany</Country></OrgAddress></Affiliation><Affiliation ID="Aff4"><OrgName>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP)</OrgName><OrgAddress><Postcode>D-14476</Postcode><City>Golm</City><Country>Germany</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En"><Heading>Abstract</Heading><Para><Emphasis Type="BoldItalic">Purpose</Emphasis>. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues.</Para><Para><Emphasis Type="BoldItalic">Methods</Emphasis>. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core.</Para><Para><Emphasis Type="BoldItalic">Results</Emphasis>. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. <Emphasis Type="Italic">In vivo</Emphasis> rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant.</Para><Para><Emphasis Type="BoldItalic">Conclusions</Emphasis>. A strategy for <Emphasis Type="Italic">in vivo</Emphasis> gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.</Para></Abstract><KeywordGroup Language="En"><Keyword>β-gal expression</Keyword><Keyword>human urokinase plasminogen activator</Keyword><Keyword>nanoparticle-mediated gene transfer</Keyword><Keyword>vascular gene transfer</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Polyelectrolyte Nanoparticles Mediate Vascular Gene Delivery</title></titleInfo><name type="personal"><namePart type="given">Sergey</namePart><namePart type="family">Zaitsev</namePart><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Régis</namePart><namePart type="family">Cartier</namePart><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Oleg</namePart><namePart type="family">Vyborov</namePart><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gleb</namePart><namePart type="family">Sukhorukov</namePart><affiliation>Max Planck Institute of Colloids and Surfaces, D-14476, Golm, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernd-Reiner</namePart><namePart type="family">Paulke</namePart><affiliation>Fraunhofer Institute for Applied Polymer Research (Fraunhofer IAP), D-14476, Golm, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Annekathrin</namePart><namePart type="family">Haberland</namePart><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yelena</namePart><namePart type="family">Parfyonova</namePart><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vsevolod</namePart><namePart type="family">Tkachuk</namePart><affiliation>Institute of Cytology of the Russian Academy of Sciences, 194064, St. Petersburg, Russia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Böttger</namePart><affiliation>Franz Volhard Clinic, HELIOS Klinikum-Berlin at the Max Delbrück Center for Molecular Medicine (MDC), D-13125, Berlin-Buch, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" 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>Kluwer Academic Publishers-Plenum Publishers</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2004-09-01</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: Purpose. The purpose is to develop a non-viral gene delivery system that meets the requirements of colloidal stability of DNA complexes expressed in terms of no particle aggregation under physiologic conditions. The system should be used to transfect cardiovascular tissues. Methods. We used a strategy based on the formation of polyelectrolyte nanoparticles by deposition of alternatively charged polyelectrolytes onto a DNA core. Polyelectrolytes were transfer RNA as well as the synthetic polyanion, polyvinyl sulfate (PVS), and the polycation polyethylenimine (PEI). The PEI/DNA complex formed the DNA core. Results. We observed that the DNA is condensed by polycations and further packaged by association with a polyanion. These nanoparticles exhibited negative surface charge and low aggregation tendency. In vivo rat carotid artery experiments revealed high transfection efficiency, not only with the reporter gene but also with the gene encoding human urokinase plasminogen activator (Hu-uPA). Hu-uPA is one of the proteins involved in the recovery of the blood vessels after balloon catheter injury and therefore clinically relevant. Conclusions. A strategy for in vivo gene transfer is proposed that uses the incorporation of polyanions as RNA or PVS into PEI/DNA complexes in order to overcome colloidal instability and to generate a negative surface charge. The particles proved to be transfectionally active in vascular gene transfer.</abstract><subject lang="en"><topic>β-gal expression</topic><topic>human urokinase plasminogen activator</topic><topic>nanoparticle-mediated gene transfer</topic><topic>vascular gene transfer</topic></subject><relatedItem type="host"><titleInfo><title>Pharmaceutical Research</title><subTitle>An Official Journal of the American Association of Pharmaceutical Scientists</subTitle></titleInfo><titleInfo type="abbreviated"><title>Pharm Res</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>Springer</publisher><dateIssued encoding="w3cdtf">2004-09-01</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><subject><genre>Biomedicine</genre><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Biochemistry, general</topic><topic>Medical Law</topic><topic>Biomedical Engineering</topic></subject><identifier type="ISSN">0724-8741</identifier><identifier type="eISSN">1573-904X</identifier><identifier type="JournalID">11095</identifier><identifier type="IssueArticleCount">30</identifier><identifier type="VolumeIssueCount">12</identifier><part><date>2004</date><detail type="volume"><number>21</number><caption>vol.</caption></detail><detail type="issue"><number>9</number><caption>no.</caption></detail><extent unit="pages"><start>1656</start><end>1661</end></extent></part><recordInfo><recordOrigin>Springer Science+Business Media, Inc., 2004</recordOrigin></recordInfo></relatedItem><identifier type="istex">122722A2D7887D9C17FB2589D4276052190E49C3</identifier><identifier type="ark">ark:/67375/VQC-12XTRJBH-N</identifier><identifier type="DOI">10.1023/B:PHAM.0000041462.19131.08</identifier><identifier type="ArticleID">492480</identifier><identifier type="ArticleID">Art20</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media, Inc., 2004</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer Science+Business Media, Inc., 2004</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-12XTRJBH-N/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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