Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene
Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. The purpose of the present study was to define whether gene transfer of multiple genes is a feasible approach and whether this approach would be more effective than the single transfer...
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| Veröffentlicht in: | Gene therapy 2004-05, Vol.11 (10), p.847-855 |
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| description | Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. The purpose of the present study was to define whether gene transfer of multiple genes is a feasible approach and whether this approach would be more effective than the single transfer of cDNA. Rats were inflicted an acute wound and divided into four groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 μg, vehicle), or liposomes plus the insulin like-growth factor-I (IGF-I)cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the keratinocyte growth factor (KGF) cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the IGF-I/KGF cDNA (2.2 μg) and Lac Z gene (0.22 μg). Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, dermal and epidermal regeneration. IGF-I/KGF cDNA transfer increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example,by increasing IGFBP-3, P |
| doi_str_mv | 10.1038/sj.gt.3302229 |
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The purpose of the present study was to define whether gene transfer of multiple genes is a feasible approach and whether this approach would be more effective than the single transfer of cDNA. Rats were inflicted an acute wound and divided into four groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 μg, vehicle), or liposomes plus the insulin like-growth factor-I (IGF-I)cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the keratinocyte growth factor (KGF) cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the IGF-I/KGF cDNA (2.2 μg) and Lac Z gene (0.22 μg). Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, dermal and epidermal regeneration. IGF-I/KGF cDNA transfer increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example,by increasing IGFBP-3, P<0.05. IGF-I/KGF cDNA gene transfer improved epidermal regeneration by exhibiting the most rapid area and linear wound re-epithelization by almost 250% compared to control and each growth factor given individually, P<0.001, which was probably due to promitogenic and antiapoptotic effects on basal keratinocytes when compared to controls, P<0.001. Dermal regeneration was improved in IGF-I/KGF cDNA-treated animals by an increased collagen deposition and morphology when compared with vehicle, IGF-I and KGF, P<0.001. IGF-I/KGF cDNA increased VEGF concentrations and thus neovascularization when compared with vehicle, IGF-I and KGF, P<0.001. In the present study, we showed that exogenous gene transfer of multiple cDNA sequences have an additive effect on intracellular and biological responses when compared to the same gene administered as a single cDNA sequence. Our findings demonstrate that gene therapy with multiple genes is feasible, and that the gene transfer of multiple genes can enhance and accelerate physiologic and biological effects.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302229</identifier><identifier>PMID: 14961069</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Apoptosis - genetics ; Applied cell therapy and gene therapy ; beta-Galactosidase - genetics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cell Biology ; Cell Division - genetics ; Collagen ; Collagen - metabolism ; DNA, Complementary - genetics ; Epithelial Cells - pathology ; Feasibility Studies ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Gene Transfer Techniques ; Genes ; Growth factors ; Growth Substances - genetics ; Growth Substances - metabolism ; Health. Pharmaceutical industry ; Human Genetics ; Industrial applications and implications. Economical aspects ; Insulin ; Insulin-Like Growth Factor Binding Protein 3 - genetics ; Insulin-Like Growth Factor Binding Protein 3 - metabolism ; Insulin-like growth factor I ; Insulin-like growth factor-binding protein 3 ; Keratinocyte growth factor ; Keratinocytes ; Liposomes ; Male ; Medical sciences ; Molecular modelling ; Nanotechnology ; Neovascularization, Physiologic ; Rats ; Rats, Sprague-Dawley ; research-article ; Skin - blood supply ; Skin - injuries ; Skin - metabolism ; Skin - pathology ; Transfection ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Vascular endothelial growth factor ; Vascularization ; Wound Healing ; Wounds</subject><ispartof>Gene therapy, 2004-05, Vol.11 (10), p.847-855</ispartof><rights>Springer Nature Limited 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-c53b89c92624974474fc845ba6c31b8125583beaf74d33d1022d29e3d729b4993</citedby><cites>FETCH-LOGICAL-c570t-c53b89c92624974474fc845ba6c31b8125583beaf74d33d1022d29e3d729b4993</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.gt.3302229$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302229$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15727378$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14961069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeschke, M G</creatorcontrib><creatorcontrib>Klein, D</creatorcontrib><title>Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. The purpose of the present study was to define whether gene transfer of multiple genes is a feasible approach and whether this approach would be more effective than the single transfer of cDNA. Rats were inflicted an acute wound and divided into four groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 μg, vehicle), or liposomes plus the insulin like-growth factor-I (IGF-I)cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the keratinocyte growth factor (KGF) cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the IGF-I/KGF cDNA (2.2 μg) and Lac Z gene (0.22 μg). Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, dermal and epidermal regeneration. IGF-I/KGF cDNA transfer increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example,by increasing IGFBP-3, P<0.05. IGF-I/KGF cDNA gene transfer improved epidermal regeneration by exhibiting the most rapid area and linear wound re-epithelization by almost 250% compared to control and each growth factor given individually, P<0.001, which was probably due to promitogenic and antiapoptotic effects on basal keratinocytes when compared to controls, P<0.001. Dermal regeneration was improved in IGF-I/KGF cDNA-treated animals by an increased collagen deposition and morphology when compared with vehicle, IGF-I and KGF, P<0.001. IGF-I/KGF cDNA increased VEGF concentrations and thus neovascularization when compared with vehicle, IGF-I and KGF, P<0.001. In the present study, we showed that exogenous gene transfer of multiple cDNA sequences have an additive effect on intracellular and biological responses when compared to the same gene administered as a single cDNA sequence. Our findings demonstrate that gene therapy with multiple genes is feasible, and that the gene transfer of multiple genes can enhance and accelerate physiologic and biological effects.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Applied cell therapy and gene therapy</subject><subject>beta-Galactosidase - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cell Biology</subject><subject>Cell Division - genetics</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>DNA, Complementary - genetics</subject><subject>Epithelial Cells - pathology</subject><subject>Feasibility Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Growth Substances - genetics</subject><subject>Growth Substances - metabolism</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Insulin</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - genetics</subject><subject>Insulin-Like Growth Factor Binding Protein 3 - metabolism</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-like growth factor-binding protein 3</subject><subject>Keratinocyte growth factor</subject><subject>Keratinocytes</subject><subject>Liposomes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular modelling</subject><subject>Nanotechnology</subject><subject>Neovascularization, Physiologic</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>research-article</subject><subject>Skin - blood supply</subject><subject>Skin - injuries</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Transfection</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Vascular endothelial growth factor</subject><subject>Vascularization</subject><subject>Wound Healing</subject><subject>Wounds</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0tuL1DAUB-AiijuuPvqoFMUFHzrm1lwel8XLwoDg5TmkadLJ0CZjkor-92ad6jjKIoUUer6T5hdOVT2GYA0B5q_Sbj3kNcYAISTuVCtIGG1aQtHdagUEFQ2DiJ9VD1LaAQAI4-h-dQaJoBBQsarkxu1DCpMa68F4U-eofLIm1sHW0zxmtx_Nz0qqXaqnEE1trDU6u68Fb5X_t03VyflhaXtY3bNqTObR8j6vPr95_enqXbN5__b66nLT6JaBXFbccaEFoogIRggjVnPSdopqDDsOUdty3BllGekx7mFJ2yNhcM-Q6IgQ-Ly6OOy7j-HLbFKWk0vajKPyJsxJMigABZD-F0ImKIOEF_j8L7gLc_QlhESUEIopZ21Rz25VkDMECGIFrQ9oUKORzttQ7kuXpzeT08Eb68r3S8gRbxHgN4d8edJQTDbf8qDmlOT1xw-n9uIPuzVqzNsUxjm74NMpbA5Qx5BSNFbuo5tU_C4hkDezJNNODlkus1T80yXa3E2mP-pleAp4sQCVtBptmQHt0tG1rGRn_Bg_lZIfTDze0W1_fnJo8CrP0fze8Vf9B5Yy5n0</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Jeschke, M G</creator><creator>Klein, D</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</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>8G5</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene</title><author>Jeschke, M G ; Klein, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-c53b89c92624974474fc845ba6c31b8125583beaf74d33d1022d29e3d729b4993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Applied cell therapy and gene therapy</topic><topic>beta-Galactosidase - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cell Biology</topic><topic>Cell Division - genetics</topic><topic>Collagen</topic><topic>Collagen - metabolism</topic><topic>DNA, Complementary - genetics</topic><topic>Epithelial Cells - pathology</topic><topic>Feasibility Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Growth Substances - genetics</topic><topic>Growth Substances - metabolism</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Insulin</topic><topic>Insulin-Like Growth Factor Binding Protein 3 - genetics</topic><topic>Insulin-Like Growth Factor Binding Protein 3 - metabolism</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-like growth factor-binding protein 3</topic><topic>Keratinocyte growth factor</topic><topic>Keratinocytes</topic><topic>Liposomes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular modelling</topic><topic>Nanotechnology</topic><topic>Neovascularization, Physiologic</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>research-article</topic><topic>Skin - blood supply</topic><topic>Skin - injuries</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Transfection</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Vascular endothelial growth factor</topic><topic>Vascularization</topic><topic>Wound Healing</topic><topic>Wounds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jeschke, M G</creatorcontrib><creatorcontrib>Klein, D</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>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>Research Library (Alumni Edition)</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>Research Library Prep</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jeschke, M G</au><au>Klein, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>11</volume><issue>10</issue><spage>847</spage><epage>855</epage><pages>847-855</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. The purpose of the present study was to define whether gene transfer of multiple genes is a feasible approach and whether this approach would be more effective than the single transfer of cDNA. Rats were inflicted an acute wound and divided into four groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 μg, vehicle), or liposomes plus the insulin like-growth factor-I (IGF-I)cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the keratinocyte growth factor (KGF) cDNA (2.2 μg) and Lac Z gene (0.22 μg), or liposomes plus the IGF-I/KGF cDNA (2.2 μg) and Lac Z gene (0.22 μg). Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, dermal and epidermal regeneration. IGF-I/KGF cDNA transfer increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example,by increasing IGFBP-3, P<0.05. IGF-I/KGF cDNA gene transfer improved epidermal regeneration by exhibiting the most rapid area and linear wound re-epithelization by almost 250% compared to control and each growth factor given individually, P<0.001, which was probably due to promitogenic and antiapoptotic effects on basal keratinocytes when compared to controls, P<0.001. Dermal regeneration was improved in IGF-I/KGF cDNA-treated animals by an increased collagen deposition and morphology when compared with vehicle, IGF-I and KGF, P<0.001. IGF-I/KGF cDNA increased VEGF concentrations and thus neovascularization when compared with vehicle, IGF-I and KGF, P<0.001. In the present study, we showed that exogenous gene transfer of multiple cDNA sequences have an additive effect on intracellular and biological responses when compared to the same gene administered as a single cDNA sequence. Our findings demonstrate that gene therapy with multiple genes is feasible, and that the gene transfer of multiple genes can enhance and accelerate physiologic and biological effects.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14961069</pmid><doi>10.1038/sj.gt.3302229</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Apoptosis - genetics Applied cell therapy and gene therapy beta-Galactosidase - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cell Biology Cell Division - genetics Collagen Collagen - metabolism DNA, Complementary - genetics Epithelial Cells - pathology Feasibility Studies Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Gene Transfer Techniques Genes Growth factors Growth Substances - genetics Growth Substances - metabolism Health. Pharmaceutical industry Human Genetics Industrial applications and implications. Economical aspects Insulin Insulin-Like Growth Factor Binding Protein 3 - genetics Insulin-Like Growth Factor Binding Protein 3 - metabolism Insulin-like growth factor I Insulin-like growth factor-binding protein 3 Keratinocyte growth factor Keratinocytes Liposomes Male Medical sciences Molecular modelling Nanotechnology Neovascularization, Physiologic Rats Rats, Sprague-Dawley research-article Skin - blood supply Skin - injuries Skin - metabolism Skin - pathology Transfection Transfusions. Complications. Transfusion reactions. Cell and gene therapy Vascular endothelial growth factor Vascularization Wound Healing Wounds |
| title | Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene |
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