Replicative retroviral vectors for cancer gene therapy
Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two...
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creator | Solly, Sounkary K Trajcevski, Stephane Frisén, Charlotte Holzer, Georg W Nelson, Elisabeth Clerc, Béatrice Abordo-Adesida, Evelyn Castro, Maria Lowenstein, Pedro Klatzmann, David |
description | Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two replicative retrovirus-derived vector systems: one inherently replicative vector, and one defective vector propagated by a helper retrovirus.
In vitro
, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced |
doi_str_mv | 10.1038/sj.cgt.7700521 |
format | Article |
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In vitro
, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced <1% under similar conditions. It is noteworthy that viral propagation could be efficiently blocked by azido-thymidine,
in vitro
and
in vivo
. In a model of established brain tumors treated with suicide genes, replicative retroviral vectors (RRVs) were approximately 1000 times more efficient than defective adenoviral vectors. These results demonstrate the advantage and potential of RRVs and strongly support their development for cancer gene therapy.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/sj.cgt.7700521</identifier><identifier>PMID: 12489026</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>3T3 Cells ; Adenoviridae - genetics ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Control ; Gene Expression ; Gene Therapy ; Gene Transfer Techniques ; Genetic aspects ; Genetic Therapy - methods ; Genetic Vectors ; Green Fluorescent Proteins ; Health aspects ; Humans ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Moloney murine leukemia virus - genetics ; Neoplasms - genetics ; Neoplasms - therapy ; Neoplasms - virology ; original-article ; Rats ; Rats, Inbred Lew ; Recombinant Fusion Proteins - metabolism ; Retroviruses ; Reverse Transcriptase Polymerase Chain Reaction ; Risk factors ; Tumor Cells, Cultured ; Virus Replication</subject><ispartof>Cancer gene therapy, 2003-01, Vol.10 (1), p.30-39</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-2df970269325ea427cda94c0a8c19d71d77e33032868d59105c52802fcb989563</citedby><cites>FETCH-LOGICAL-c487t-2df970269325ea427cda94c0a8c19d71d77e33032868d59105c52802fcb989563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.cgt.7700521$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.cgt.7700521$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12489026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Solly, Sounkary K</creatorcontrib><creatorcontrib>Trajcevski, Stephane</creatorcontrib><creatorcontrib>Frisén, Charlotte</creatorcontrib><creatorcontrib>Holzer, Georg W</creatorcontrib><creatorcontrib>Nelson, Elisabeth</creatorcontrib><creatorcontrib>Clerc, Béatrice</creatorcontrib><creatorcontrib>Abordo-Adesida, Evelyn</creatorcontrib><creatorcontrib>Castro, Maria</creatorcontrib><creatorcontrib>Lowenstein, Pedro</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><title>Replicative retroviral vectors for cancer gene therapy</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><addtitle>Cancer Gene Ther</addtitle><description>Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two replicative retrovirus-derived vector systems: one inherently replicative vector, and one defective vector propagated by a helper retrovirus.
In vitro
, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced <1% under similar conditions. It is noteworthy that viral propagation could be efficiently blocked by azido-thymidine,
in vitro
and
in vivo
. In a model of established brain tumors treated with suicide genes, replicative retroviral vectors (RRVs) were approximately 1000 times more efficient than defective adenoviral vectors. These results demonstrate the advantage and potential of RRVs and strongly support their development for cancer gene therapy.</description><subject>3T3 Cells</subject><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Control</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Green Fluorescent Proteins</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Nude</subject><subject>Moloney murine leukemia virus - genetics</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - therapy</subject><subject>Neoplasms - virology</subject><subject>original-article</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Retroviruses</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Risk factors</subject><subject>Tumor Cells, Cultured</subject><subject>Virus Replication</subject><issn>0929-1903</issn><issn>1476-5500</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1rGzEQxUVJaZy01x7LkkBu64ykXX0cQ2g-IFAI6Vko2llbZr1yJa0h_32V2JA2pJQ5CGZ-74nHI-QrhTkFrs7Tau4WeS4lQMvoBzKjjRR12wIckBlopmuqgR-So5RWAOUo-SdySFmjNDAxI-IeN4N3NvstVhFzDFsf7VBt0eUQU9WHWDk7OozVAkes8hKj3Tx9Jh97OyT8sn-Pyc-r7w-XN_Xdj-vby4u72jVK5pp1vZblH81Zi7Zh0nVWNw6sclR3knZSIufAmRKqazWF1rVMAevdo1a6FfyYnO18NzH8mjBls_bJ4TDYEcOUjGRKaSHZf0GqhADBoIAnb8BVmOJYQhhGZaO4foFOd9DCDmj82IccrXt2NBdUMSmkpqpQ83eoMh2uvQsj9r7s_xKc_SFYoh3yMoVhyj6M6V1nF0NKEXuziX5t45OhYJ57N2llSu9m33sRfNunmh7X2L3i-6ILcL4DUjmNC4yvsf9h-RsMCLSg</recordid><startdate>20030101</startdate><enddate>20030101</enddate><creator>Solly, Sounkary K</creator><creator>Trajcevski, Stephane</creator><creator>Frisén, Charlotte</creator><creator>Holzer, Georg W</creator><creator>Nelson, Elisabeth</creator><creator>Clerc, Béatrice</creator><creator>Abordo-Adesida, Evelyn</creator><creator>Castro, Maria</creator><creator>Lowenstein, Pedro</creator><creator>Klatzmann, David</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>20030101</creationdate><title>Replicative retroviral vectors for cancer gene therapy</title><author>Solly, Sounkary K ; Trajcevski, Stephane ; Frisén, Charlotte ; Holzer, Georg W ; Nelson, Elisabeth ; Clerc, Béatrice ; Abordo-Adesida, Evelyn ; Castro, Maria ; Lowenstein, Pedro ; Klatzmann, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-2df970269325ea427cda94c0a8c19d71d77e33032868d59105c52802fcb989563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>3T3 Cells</topic><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Control</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Green Fluorescent Proteins</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Nude</topic><topic>Moloney murine leukemia virus - genetics</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - therapy</topic><topic>Neoplasms - virology</topic><topic>original-article</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Retroviruses</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Risk factors</topic><topic>Tumor Cells, Cultured</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Solly, Sounkary K</creatorcontrib><creatorcontrib>Trajcevski, Stephane</creatorcontrib><creatorcontrib>Frisén, Charlotte</creatorcontrib><creatorcontrib>Holzer, Georg W</creatorcontrib><creatorcontrib>Nelson, Elisabeth</creatorcontrib><creatorcontrib>Clerc, Béatrice</creatorcontrib><creatorcontrib>Abordo-Adesida, Evelyn</creatorcontrib><creatorcontrib>Castro, Maria</creatorcontrib><creatorcontrib>Lowenstein, Pedro</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Solly, Sounkary K</au><au>Trajcevski, Stephane</au><au>Frisén, Charlotte</au><au>Holzer, Georg W</au><au>Nelson, Elisabeth</au><au>Clerc, Béatrice</au><au>Abordo-Adesida, Evelyn</au><au>Castro, Maria</au><au>Lowenstein, Pedro</au><au>Klatzmann, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Replicative retroviral vectors for cancer gene therapy</atitle><jtitle>Cancer gene therapy</jtitle><stitle>Cancer Gene Ther</stitle><addtitle>Cancer Gene Ther</addtitle><date>2003-01-01</date><risdate>2003</risdate><volume>10</volume><issue>1</issue><spage>30</spage><epage>39</epage><pages>30-39</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><abstract>Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two replicative retrovirus-derived vector systems: one inherently replicative vector, and one defective vector propagated by a helper retrovirus.
In vitro
, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced <1% under similar conditions. It is noteworthy that viral propagation could be efficiently blocked by azido-thymidine,
in vitro
and
in vivo
. In a model of established brain tumors treated with suicide genes, replicative retroviral vectors (RRVs) were approximately 1000 times more efficient than defective adenoviral vectors. These results demonstrate the advantage and potential of RRVs and strongly support their development for cancer gene therapy.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12489026</pmid><doi>10.1038/sj.cgt.7700521</doi><tpages>10</tpages></addata></record> |
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source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
subjects | 3T3 Cells Adenoviridae - genetics Animals Biomedical and Life Sciences Biomedicine Cancer Control Gene Expression Gene Therapy Gene Transfer Techniques Genetic aspects Genetic Therapy - methods Genetic Vectors Green Fluorescent Proteins Health aspects Humans Luminescent Proteins - genetics Luminescent Proteins - metabolism Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Moloney murine leukemia virus - genetics Neoplasms - genetics Neoplasms - therapy Neoplasms - virology original-article Rats Rats, Inbred Lew Recombinant Fusion Proteins - metabolism Retroviruses Reverse Transcriptase Polymerase Chain Reaction Risk factors Tumor Cells, Cultured Virus Replication |
title | Replicative retroviral vectors for cancer gene therapy |
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