Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction
Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in...
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| Veröffentlicht in: | Human gene therapy 2012-10, Vol.23 (10), p.1031-1042 |
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| creator | MESSINA, Emily L NIENABER, Jeffrey DANESHMAND, Mani VILLAMIZAR, Nestor SAMULSKI, Jude MILANO, Carmelo BOWLES, Dawn E |
| description | Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases. |
| doi_str_mv | 10.1089/hum.2012.066 |
| format | Article |
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Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2012.066</identifier><identifier>PMID: 22680698</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Adeno-associated virus ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biotechnology ; Cell Line, Tumor ; Dependovirus - classification ; Dependovirus - drug effects ; Dependovirus - genetics ; Expression vectors ; Fibroblast growth factor ; Fibroblast growth factor 1 ; Fibroblast growth factor receptor 2 ; Fibroblast growth factor receptors ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Genetic Therapy ; Genetic Vectors - genetics ; Genotype ; Glycosaminoglycans - metabolism ; Growth factor receptors ; Health. Pharmaceutical industry ; Heparin ; Heparin - administration & dosage ; Heparin - pharmacology ; Humans ; Industrial applications and implications. Economical aspects ; Intercellular Signaling Peptides and Proteins - pharmacology ; Luciferases - metabolism ; Medical sciences ; Mice ; Receptor, Fibroblast Growth Factor, Type 2 - genetics ; Receptor, Fibroblast Growth Factor, Type 2 - metabolism ; Saphenous Vein - drug effects ; Saphenous Vein - metabolism ; Serotypes ; Serotyping ; Signal transduction ; Solubility ; Sus scrofa ; Tissue Culture Techniques ; Transduction, Genetic - methods ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Human gene therapy, 2012-10, Vol.23 (10), p.1031-1042</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright 2012, Mary Ann Liebert, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-beff73644f9170b6e9d67e757be773cda706ccee7d6b731c3c8c9ca02682ff1d3</citedby><cites>FETCH-LOGICAL-c447t-beff73644f9170b6e9d67e757be773cda706ccee7d6b731c3c8c9ca02682ff1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26507180$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22680698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MESSINA, Emily L</creatorcontrib><creatorcontrib>NIENABER, Jeffrey</creatorcontrib><creatorcontrib>DANESHMAND, Mani</creatorcontrib><creatorcontrib>VILLAMIZAR, Nestor</creatorcontrib><creatorcontrib>SAMULSKI, Jude</creatorcontrib><creatorcontrib>MILANO, Carmelo</creatorcontrib><creatorcontrib>BOWLES, Dawn E</creatorcontrib><title>Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases.</description><subject>Adeno-associated virus</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cell Line, Tumor</subject><subject>Dependovirus - classification</subject><subject>Dependovirus - drug effects</subject><subject>Dependovirus - genetics</subject><subject>Expression vectors</subject><subject>Fibroblast growth factor</subject><subject>Fibroblast growth factor 1</subject><subject>Fibroblast growth factor receptor 2</subject><subject>Fibroblast growth factor receptors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors - genetics</subject><subject>Genotype</subject><subject>Glycosaminoglycans - metabolism</subject><subject>Growth factor receptors</subject><subject>Health. Pharmaceutical industry</subject><subject>Heparin</subject><subject>Heparin - administration & dosage</subject><subject>Heparin - pharmacology</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>Luciferases - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Receptor, Fibroblast Growth Factor, Type 2 - genetics</subject><subject>Receptor, Fibroblast Growth Factor, Type 2 - metabolism</subject><subject>Saphenous Vein - drug effects</subject><subject>Saphenous Vein - metabolism</subject><subject>Serotypes</subject><subject>Serotyping</subject><subject>Signal transduction</subject><subject>Solubility</subject><subject>Sus scrofa</subject><subject>Tissue Culture Techniques</subject><subject>Transduction, Genetic - methods</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEoqVw44x8QeLQLP5I7OSCtKy6BakSEv24Wo4z3jVK7GA70P4Tfi4OXQqcOHlkP340M29RvCR4RXDTvt3P44piQleY80fFMalrUYqK0se5xhUrMavoUfEsxi8YE1Zz8bQ4opQ3mLfNcfFj3YPz5TpGr61K0KMbG9SAbkAnHyJ6r2K-8w5dQvDpbgLEOnQdAW38OHkHLkXkDUp7QFvbBd8NKiZ0Hvz3tEdbtUjQZ9AwLcWl3Tk1WLf79XuAW2Ty7ZkxVttsQldBudjPOlnvnhdPjBoivDicJ8X19uxq86G8-HT-cbO-KHVViVR2YIxgvKpMSwTuOLQ9FyBq0YEQTPdKYK41gOh5JxjRTDe61QrnBVBjSM9Oinf33mnuRuh17iPPL6dgRxXupFdW_vvi7F7u_DfJKkFr0mTBm4Mg-K8zxCRHGzUMg3Lg5ygJpYRUtBHk_2gG25pgtlhP71EdfIwBzENHBMsld5lzl0vuMuee8Vd_T_EA_w46A68PgIpaDSZvWtv4h-M1FqTB7CfTHrmb</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>MESSINA, Emily L</creator><creator>NIENABER, Jeffrey</creator><creator>DANESHMAND, Mani</creator><creator>VILLAMIZAR, Nestor</creator><creator>SAMULSKI, Jude</creator><creator>MILANO, Carmelo</creator><creator>BOWLES, Dawn E</creator><general>Liebert</general><general>Mary Ann Liebert, Inc</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>7X8</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121001</creationdate><title>Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction</title><author>MESSINA, Emily L ; NIENABER, Jeffrey ; DANESHMAND, Mani ; VILLAMIZAR, Nestor ; SAMULSKI, Jude ; MILANO, Carmelo ; BOWLES, Dawn E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-beff73644f9170b6e9d67e757be773cda706ccee7d6b731c3c8c9ca02682ff1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adeno-associated virus</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cell Line, Tumor</topic><topic>Dependovirus - classification</topic><topic>Dependovirus - drug effects</topic><topic>Dependovirus - genetics</topic><topic>Expression vectors</topic><topic>Fibroblast growth factor</topic><topic>Fibroblast growth factor 1</topic><topic>Fibroblast growth factor receptor 2</topic><topic>Fibroblast growth factor receptors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors - genetics</topic><topic>Genotype</topic><topic>Glycosaminoglycans - metabolism</topic><topic>Growth factor receptors</topic><topic>Health. Pharmaceutical industry</topic><topic>Heparin</topic><topic>Heparin - administration & dosage</topic><topic>Heparin - pharmacology</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Intercellular Signaling Peptides and Proteins - pharmacology</topic><topic>Luciferases - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Receptor, Fibroblast Growth Factor, Type 2 - genetics</topic><topic>Receptor, Fibroblast Growth Factor, Type 2 - metabolism</topic><topic>Saphenous Vein - drug effects</topic><topic>Saphenous Vein - metabolism</topic><topic>Serotypes</topic><topic>Serotyping</topic><topic>Signal transduction</topic><topic>Solubility</topic><topic>Sus scrofa</topic><topic>Tissue Culture Techniques</topic><topic>Transduction, Genetic - methods</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MESSINA, Emily L</creatorcontrib><creatorcontrib>NIENABER, Jeffrey</creatorcontrib><creatorcontrib>DANESHMAND, Mani</creatorcontrib><creatorcontrib>VILLAMIZAR, Nestor</creatorcontrib><creatorcontrib>SAMULSKI, Jude</creatorcontrib><creatorcontrib>MILANO, Carmelo</creatorcontrib><creatorcontrib>BOWLES, Dawn E</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MESSINA, Emily L</au><au>NIENABER, Jeffrey</au><au>DANESHMAND, Mani</au><au>VILLAMIZAR, Nestor</au><au>SAMULSKI, Jude</au><au>MILANO, Carmelo</au><au>BOWLES, Dawn E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>23</volume><issue>10</issue><spage>1031</spage><epage>1042</epage><pages>1031-1042</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><coden>HGTHE3</coden><abstract>Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>22680698</pmid><doi>10.1089/hum.2012.066</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Human gene therapy, 2012-10, Vol.23 (10), p.1031-1042 |
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| subjects | Adeno-associated virus Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Biological and medical sciences Biotechnology Cell Line, Tumor Dependovirus - classification Dependovirus - drug effects Dependovirus - genetics Expression vectors Fibroblast growth factor Fibroblast growth factor 1 Fibroblast growth factor receptor 2 Fibroblast growth factor receptors Fundamental and applied biological sciences. Psychology Gene therapy Genetic Therapy Genetic Vectors - genetics Genotype Glycosaminoglycans - metabolism Growth factor receptors Health. Pharmaceutical industry Heparin Heparin - administration & dosage Heparin - pharmacology Humans Industrial applications and implications. Economical aspects Intercellular Signaling Peptides and Proteins - pharmacology Luciferases - metabolism Medical sciences Mice Receptor, Fibroblast Growth Factor, Type 2 - genetics Receptor, Fibroblast Growth Factor, Type 2 - metabolism Saphenous Vein - drug effects Saphenous Vein - metabolism Serotypes Serotyping Signal transduction Solubility Sus scrofa Tissue Culture Techniques Transduction, Genetic - methods Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction |
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