Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy
Abstract The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems d...
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| Veröffentlicht in: | Journal of drug targeting 1998, Vol.5 (3), p.163-169 |
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| container_end_page | 169 |
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| container_title | Journal of drug targeting |
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| creator | Aronsohn, A. I. Hughes, J. A. |
| description | Abstract
The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP-:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy. |
| doi_str_mv | 10.3109/10611869808995871 |
| format | Article |
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The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP-:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.</description><identifier>ISSN: 1061-186X</identifier><identifier>EISSN: 1029-2330</identifier><identifier>DOI: 10.3109/10611869808995871</identifier><identifier>PMID: 9606006</identifier><language>eng</language><publisher>Abington: Informa UK Ltd</publisher><subject>Amino Acid Sequence ; Biological and medical sciences ; Cationic liposomes ; Cations ; Cell Line ; DNA - administration & dosage ; gene therapy ; General pharmacology ; Genetic Therapy ; Liposomes ; Medical sciences ; Microscopy, Electron ; Nuclear Localization Signals ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Plasmids ; Protein Sorting Signals - analysis ; signal peptides</subject><ispartof>Journal of drug targeting, 1998, Vol.5 (3), p.163-169</ispartof><rights>1998 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1998</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-3f260e5b56275dcdc2efc970a8e736cd556d0d383ffa92debae93afd10d17d2c3</citedby><cites>FETCH-LOGICAL-c461t-3f260e5b56275dcdc2efc970a8e736cd556d0d383ffa92debae93afd10d17d2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/10611869808995871$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/10611869808995871$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2236903$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9606006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aronsohn, A. I.</creatorcontrib><creatorcontrib>Hughes, J. A.</creatorcontrib><title>Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy</title><title>Journal of drug targeting</title><addtitle>J Drug Target</addtitle><description>Abstract
The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP-:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.</description><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Cationic liposomes</subject><subject>Cations</subject><subject>Cell Line</subject><subject>DNA - administration & dosage</subject><subject>gene therapy</subject><subject>General pharmacology</subject><subject>Genetic Therapy</subject><subject>Liposomes</subject><subject>Medical sciences</subject><subject>Microscopy, Electron</subject><subject>Nuclear Localization Signals</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasmids</subject><subject>Protein Sorting Signals - analysis</subject><subject>signal peptides</subject><issn>1061-186X</issn><issn>1029-2330</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1r3DAQhkVoSdI0PyCHgA-lN7cjKZYt2ktZ0rSw_YBuIDczK42yCrLlSDZl--vrdLeBUshJgvd5B80jxs44vJEc9FsOivNG6QYaraum5gfsmIPQpZASnj3cFS9n4OaIvcj5DoBLxeGQHWoFCkAds9XXyQTCVCyjweB_4ehjX_zwtz2G4jsNo7eUi8t-g72hYvEn9qZY-iHm2FH5hazHkWxxRT0Vqw0lHLYv2XOHIdPp_jxh1x8vV4tP5fLb1efFh2VpLhQfS-mEAqrWlRJ1ZY01gpzRNWBDtVTGVpWyYGUjnUMtLK2RtERnOVheW2HkCXu9mzukeD9RHtvOZ0MhYE9xyi1XFyBUo2aQ70CTYs6JXDsk32HathzaB5Ptfybnzvl--LTuyD429urm_NU-xzyrc2k25PMjJoRUGuSMvd9hvncxdfgzpmDbEbchpr8d-dQr3v1T3xCGcWMwUXsXpzT_Un5ih9-riKEv</recordid><startdate>1998</startdate><enddate>1998</enddate><creator>Aronsohn, A. I.</creator><creator>Hughes, J. A.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>1998</creationdate><title>Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy</title><author>Aronsohn, A. I. ; Hughes, J. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-3f260e5b56275dcdc2efc970a8e736cd556d0d383ffa92debae93afd10d17d2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>Cationic liposomes</topic><topic>Cations</topic><topic>Cell Line</topic><topic>DNA - administration & dosage</topic><topic>gene therapy</topic><topic>General pharmacology</topic><topic>Genetic Therapy</topic><topic>Liposomes</topic><topic>Medical sciences</topic><topic>Microscopy, Electron</topic><topic>Nuclear Localization Signals</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasmids</topic><topic>Protein Sorting Signals - analysis</topic><topic>signal peptides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aronsohn, A. I.</creatorcontrib><creatorcontrib>Hughes, J. A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of drug targeting</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aronsohn, A. I.</au><au>Hughes, J. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy</atitle><jtitle>Journal of drug targeting</jtitle><addtitle>J Drug Target</addtitle><date>1998</date><risdate>1998</risdate><volume>5</volume><issue>3</issue><spage>163</spage><epage>169</epage><pages>163-169</pages><issn>1061-186X</issn><eissn>1029-2330</eissn><abstract>Abstract
The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP-:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.</abstract><cop>Abington</cop><pub>Informa UK Ltd</pub><pmid>9606006</pmid><doi>10.3109/10611869808995871</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of drug targeting, 1998, Vol.5 (3), p.163-169 |
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| language | eng |
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| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete |
| subjects | Amino Acid Sequence Biological and medical sciences Cationic liposomes Cations Cell Line DNA - administration & dosage gene therapy General pharmacology Genetic Therapy Liposomes Medical sciences Microscopy, Electron Nuclear Localization Signals Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Plasmids Protein Sorting Signals - analysis signal peptides |
| title | Nuclear Localization Signal Peptides Enhance Cationic Liposome-Mediated Gene Therapy |
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