Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy
Identifieur interne : 008F69 ( Main/Exploration ); précédent : 008F68; suivant : 008F70Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy
Auteurs : Annette Deichmann [Allemagne] ; Salima Hacein-Bey-Abina [France] ; Manfred Schmidt [Allemagne] ; Alexandrine Garrigue [France] ; Martijn H. Brugman [Pays-Bas] ; Jingqiong Hu ; Hanno Glimm [Allemagne] ; Gabor Gyapay [France] ; Bernard Prum [France] ; Christopher C. Fraser [États-Unis] ; Nicolas Fischer [France] ; Kerstin Schwarzwaelder [Allemagne] ; Maria-Luise Siegler ; Dick De Ridder [Pays-Bas] ; Karin Pike-Overzet [Pays-Bas] ; Steven J. Howe [Royaume-Uni] ; Adrian J. Thrasher [Royaume-Uni] ; Gerard Wagemaker [Pays-Bas] ; Ulrich Abel [Allemagne] ; Frank J. T. Staal [Pays-Bas] ; Eric Delabesse [France] ; Jean-Luc Villeval [France] ; Bruce Aronow [États-Unis] ; Christophe Hue [France] ; Claudia Prinz ; Manuela Wissler [Allemagne] ; Chuck Klanke [États-Unis] ; Jean Weissenbach [France] ; Ian Alexander [Australie] ; Alain Fischer [France] ; Christof Von Kalle [Allemagne, États-Unis] ; Marina Cavazzana-Calvo [France]Source :
- Journal of Clinical Investigation [ 0021-9738 ] ; 2007.
Abstract
Recent reports have challenged the notion that retroviruses and retroviral vectors integrate randomly into the host genome. These reports pointed to a strong bias toward integration in and near gene coding regions and, for gammaretroviral vectors, around transcription start sites. Here, we report the results obtained from a large-scale mapping of 572 retroviral integration sites (RISs) isolated from cells of 9 patients with X-linked SCID (SCID-X1) treated with a retrovirus-based gene therapy protocol. Our data showed that two-thirds of insertions occurred in or very near to genes, of which more than half were highly expressed in CD34+ progenitor cells. Strikingly, one-fourth of all integrations were clustered as common integration sites (CISs). The highly significant incidence of CISs in circulating T cells and the nature of their locations indicate that insertion in many gene loci has an influence on cell engraftment, survival, and proliferation. Beyond the observed cases of insertional mutagenesis in 3 patients, these data help to elucidate the relationship between vector insertion and long-term in vivo selection of transduced cells in human patients with SCID-X1.
Url:
DOI: 10.1172/JCI31659
PubMed: 17671652
PubMed Central: 1934585
Affiliations:
- Allemagne, Australie, France, Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Bade-Wurtemberg, District de Fribourg-en-Brisgau, District de Karlsruhe, Grand Londres, Hollande-Méridionale, Massachusetts, Midi-Pyrénées, Occitanie (région administrative), Ohio, Île-de-France
- Fribourg-en-Brisgau, Heidelberg, Londres, Paris, Rotterdam, Toulouse, Évry (Essonne)
- University College de Londres
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Le document en format XML
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Brugman</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Hematology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hu, Jingqiong" sort="Hu, Jingqiong" uniqKey="Hu J" first="Jingqiong" last="Hu">Jingqiong Hu</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="Glimm, Hanno" sort="Glimm, Hanno" uniqKey="Glimm H" first="Hanno" last="Glimm">Hanno Glimm</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Gyapay, Gabor" sort="Gyapay, Gabor" uniqKey="Gyapay G" first="Gabor" last="Gyapay">Gabor Gyapay</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Génoscope and CNRS UMR8030, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Génoscope and CNRS UMR8030, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Prum, Bernard" sort="Prum, Bernard" uniqKey="Prum B" first="Bernard" last="Prum">Bernard Prum</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Laboratoire “Statistique et Génome,” UMR CNRS 8071, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire “Statistique et Génome,” UMR CNRS 8071, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Fraser, Christopher C" sort="Fraser, Christopher C" uniqKey="Fraser C" first="Christopher C." last="Fraser">Christopher C. Fraser</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Millennium Pharmaceuticals Inc., Cambridge, Massachusetts, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Millennium Pharmaceuticals Inc., Cambridge, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Fischer, Nicolas" sort="Fischer, Nicolas" uniqKey="Fischer N" first="Nicolas" last="Fischer">Nicolas Fischer</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">Laboratoire National de Métrologie et D’essais, Trappes, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire National de Métrologie et D’essais, Trappes</wicri:regionArea><wicri:noRegion>Trappes</wicri:noRegion><wicri:noRegion>Trappes</wicri:noRegion></affiliation></author><author><name sortKey="Schwarzwaelder, Kerstin" sort="Schwarzwaelder, Kerstin" uniqKey="Schwarzwaelder K" first="Kerstin" last="Schwarzwaelder">Kerstin Schwarzwaelder</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Faculty of Biology, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Faculty of Biology, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Siegler, Maria Luise" sort="Siegler, Maria Luise" uniqKey="Siegler M" first="Maria-Luise" last="Siegler">Maria-Luise Siegler</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="De Ridder, Dick" sort="De Ridder, Dick" uniqKey="De Ridder D" first="Dick" last="De Ridder">Dick De Ridder</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI31659">Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Pike Overzet, Karin" sort="Pike Overzet, Karin" uniqKey="Pike Overzet K" first="Karin" last="Pike-Overzet">Karin Pike-Overzet</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Howe, Steven J" sort="Howe, Steven J" uniqKey="Howe S" first="Steven J." last="Howe">Steven J. Howe</name><affiliation wicri:level="4"><nlm:aff id="JCI31659">Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Molecular Immunology Unit, Institute of Child Health, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J." last="Thrasher">Adrian J. Thrasher</name><affiliation wicri:level="4"><nlm:aff id="JCI31659">Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Molecular Immunology Unit, Institute of Child Health, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Clinical Immunology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Department of Clinical Immunology, Great Ormond Street Hospital for Children NHS Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Wagemaker, Gerard" sort="Wagemaker, Gerard" uniqKey="Wagemaker G" first="Gerard" last="Wagemaker">Gerard Wagemaker</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Hematology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Abel, Ulrich" sort="Abel, Ulrich" uniqKey="Abel U" first="Ulrich" last="Abel">Ulrich Abel</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Medical Biostatistics, Tumor Center Heidelberg-Mannheim, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Medical Biostatistics, Tumor Center Heidelberg-Mannheim, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Staal, Frank J T" sort="Staal, Frank J T" uniqKey="Staal F" first="Frank J. T." last="Staal">Frank J. T. Staal</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Delabesse, Eric" sort="Delabesse, Eric" uniqKey="Delabesse E" first="Eric" last="Delabesse">Eric Delabesse</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Laboratoire d’Hématologie CHU Purpan, Toulouse, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire d’Hématologie CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Villeval, Jean Luc" sort="Villeval, Jean Luc" uniqKey="Villeval J" first="Jean-Luc" last="Villeval">Jean-Luc Villeval</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">INSERM U790, Institut Gustave Roussy, Villejuif, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U790, Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Aronow, Bruce" sort="Aronow, Bruce" uniqKey="Aronow B" first="Bruce" last="Aronow">Bruce Aronow</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Bioinformatics, Children’s Hospital Medical Center, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Bioinformatics, Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Hue, Christophe" sort="Hue, Christophe" uniqKey="Hue C" first="Christophe" last="Hue">Christophe Hue</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Département de Biothérapies, Hôpital Necker, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Département de Biothérapies, Hôpital Necker, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Prinz, Claudia" sort="Prinz, Claudia" uniqKey="Prinz C" first="Claudia" last="Prinz">Claudia Prinz</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="Wissler, Manuela" sort="Wissler, Manuela" uniqKey="Wissler M" first="Manuela" last="Wissler">Manuela Wissler</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Klanke, Chuck" sort="Klanke, Chuck" uniqKey="Klanke C" first="Chuck" last="Klanke">Chuck Klanke</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Weissenbach, Jean" sort="Weissenbach, Jean" uniqKey="Weissenbach J" first="Jean" last="Weissenbach">Jean Weissenbach</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Génoscope and CNRS UMR8030, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Génoscope and CNRS UMR8030, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Alexander, Ian" sort="Alexander, Ian" uniqKey="Alexander I" first="Ian" last="Alexander">Ian Alexander</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">The Children’s Hospital at Westmead and Children’s Medical Research Institute, Sydney, New South Wales, Australia.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Children’s Hospital at Westmead and Children’s Medical Research Institute, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Necker–Enfants Malades, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Necker–Enfants Malades, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Von Kalle, Christof" sort="Von Kalle, Christof" uniqKey="Von Kalle C" first="Christof" last="Von Kalle">Christof Von Kalle</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Cavazzana Calvo, Marina" sort="Cavazzana Calvo, Marina" uniqKey="Cavazzana Calvo M" first="Marina" last="Cavazzana-Calvo">Marina Cavazzana-Calvo</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Département de Biothérapies, Hôpital Necker, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Département de Biothérapies, Hôpital Necker, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17671652</idno><idno type="pmc">1934585</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934585</idno><idno type="RBID">PMC:1934585</idno><idno type="doi">10.1172/JCI31659</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">001933</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001933</idno><idno type="wicri:Area/Pmc/Curation">001792</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001792</idno><idno type="wicri:Area/Pmc/Checkpoint">002A73</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002A73</idno><idno type="wicri:Area/Ncbi/Merge">000289</idno><idno type="wicri:Area/Ncbi/Curation">000289</idno><idno type="wicri:Area/Ncbi/Checkpoint">000289</idno><idno type="wicri:doubleKey">0021-9738:2007:Deichmann A:vector:integration:is</idno><idno type="wicri:Area/Main/Merge">009925</idno><idno type="wicri:Area/Main/Curation">008F69</idno><idno type="wicri:Area/Main/Exploration">008F69</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy</title><author><name sortKey="Deichmann, Annette" sort="Deichmann, Annette" uniqKey="Deichmann A" first="Annette" last="Deichmann">Annette Deichmann</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hacein Bey Abina, Salima" sort="Hacein Bey Abina, Salima" uniqKey="Hacein Bey Abina S" first="Salima" last="Hacein-Bey-Abina">Salima Hacein-Bey-Abina</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Département de Biothérapies, Hôpital Necker, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Département de Biothérapies, Hôpital Necker, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Schmidt, Manfred" sort="Schmidt, Manfred" uniqKey="Schmidt M" first="Manfred" last="Schmidt">Manfred Schmidt</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Garrigue, Alexandrine" sort="Garrigue, Alexandrine" uniqKey="Garrigue A" first="Alexandrine" last="Garrigue">Alexandrine Garrigue</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Brugman, Martijn H" sort="Brugman, Martijn H" uniqKey="Brugman M" first="Martijn H." last="Brugman">Martijn H. Brugman</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Hematology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hu, Jingqiong" sort="Hu, Jingqiong" uniqKey="Hu J" first="Jingqiong" last="Hu">Jingqiong Hu</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="Glimm, Hanno" sort="Glimm, Hanno" uniqKey="Glimm H" first="Hanno" last="Glimm">Hanno Glimm</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Gyapay, Gabor" sort="Gyapay, Gabor" uniqKey="Gyapay G" first="Gabor" last="Gyapay">Gabor Gyapay</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Génoscope and CNRS UMR8030, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Génoscope and CNRS UMR8030, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Prum, Bernard" sort="Prum, Bernard" uniqKey="Prum B" first="Bernard" last="Prum">Bernard Prum</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Laboratoire “Statistique et Génome,” UMR CNRS 8071, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire “Statistique et Génome,” UMR CNRS 8071, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Fraser, Christopher C" sort="Fraser, Christopher C" uniqKey="Fraser C" first="Christopher C." last="Fraser">Christopher C. Fraser</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Millennium Pharmaceuticals Inc., Cambridge, Massachusetts, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Millennium Pharmaceuticals Inc., Cambridge, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Fischer, Nicolas" sort="Fischer, Nicolas" uniqKey="Fischer N" first="Nicolas" last="Fischer">Nicolas Fischer</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">Laboratoire National de Métrologie et D’essais, Trappes, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire National de Métrologie et D’essais, Trappes</wicri:regionArea><wicri:noRegion>Trappes</wicri:noRegion><wicri:noRegion>Trappes</wicri:noRegion></affiliation></author><author><name sortKey="Schwarzwaelder, Kerstin" sort="Schwarzwaelder, Kerstin" uniqKey="Schwarzwaelder K" first="Kerstin" last="Schwarzwaelder">Kerstin Schwarzwaelder</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Faculty of Biology, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Faculty of Biology, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Siegler, Maria Luise" sort="Siegler, Maria Luise" uniqKey="Siegler M" first="Maria-Luise" last="Siegler">Maria-Luise Siegler</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="De Ridder, Dick" sort="De Ridder, Dick" uniqKey="De Ridder D" first="Dick" last="De Ridder">Dick De Ridder</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI31659">Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft</wicri:regionArea><wicri:noRegion>Delft</wicri:noRegion></affiliation></author><author><name sortKey="Pike Overzet, Karin" sort="Pike Overzet, Karin" uniqKey="Pike Overzet K" first="Karin" last="Pike-Overzet">Karin Pike-Overzet</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Howe, Steven J" sort="Howe, Steven J" uniqKey="Howe S" first="Steven J." last="Howe">Steven J. Howe</name><affiliation wicri:level="4"><nlm:aff id="JCI31659">Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Molecular Immunology Unit, Institute of Child Health, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">University College de Londres</orgName></affiliation></author><author><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J." last="Thrasher">Adrian J. Thrasher</name><affiliation wicri:level="4"><nlm:aff id="JCI31659">Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Molecular Immunology Unit, Institute of Child Health, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Clinical Immunology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Department of Clinical Immunology, Great Ormond Street Hospital for Children NHS Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Wagemaker, Gerard" sort="Wagemaker, Gerard" uniqKey="Wagemaker G" first="Gerard" last="Wagemaker">Gerard Wagemaker</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Hematology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Abel, Ulrich" sort="Abel, Ulrich" uniqKey="Abel U" first="Ulrich" last="Abel">Ulrich Abel</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Medical Biostatistics, Tumor Center Heidelberg-Mannheim, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Medical Biostatistics, Tumor Center Heidelberg-Mannheim, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Staal, Frank J T" sort="Staal, Frank J T" uniqKey="Staal F" first="Frank J. T." last="Staal">Frank J. T. Staal</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Delabesse, Eric" sort="Delabesse, Eric" uniqKey="Delabesse E" first="Eric" last="Delabesse">Eric Delabesse</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Laboratoire d’Hématologie CHU Purpan, Toulouse, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratoire d’Hématologie CHU Purpan, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Villeval, Jean Luc" sort="Villeval, Jean Luc" uniqKey="Villeval J" first="Jean-Luc" last="Villeval">Jean-Luc Villeval</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">INSERM U790, Institut Gustave Roussy, Villejuif, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U790, Institut Gustave Roussy, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Aronow, Bruce" sort="Aronow, Bruce" uniqKey="Aronow B" first="Bruce" last="Aronow">Bruce Aronow</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Bioinformatics, Children’s Hospital Medical Center, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Bioinformatics, Children’s Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Hue, Christophe" sort="Hue, Christophe" uniqKey="Hue C" first="Christophe" last="Hue">Christophe Hue</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Département de Biothérapies, Hôpital Necker, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Département de Biothérapies, Hôpital Necker, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Prinz, Claudia" sort="Prinz, Claudia" uniqKey="Prinz C" first="Claudia" last="Prinz">Claudia Prinz</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation></author><author><name sortKey="Wissler, Manuela" sort="Wissler, Manuela" uniqKey="Wissler M" first="Manuela" last="Wissler">Manuela Wissler</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Klanke, Chuck" sort="Klanke, Chuck" uniqKey="Klanke C" first="Chuck" last="Klanke">Chuck Klanke</name><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Weissenbach, Jean" sort="Weissenbach, Jean" uniqKey="Weissenbach J" first="Jean" last="Weissenbach">Jean Weissenbach</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">Génoscope and CNRS UMR8030, Evry, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Génoscope and CNRS UMR8030, Evry</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Alexander, Ian" sort="Alexander, Ian" uniqKey="Alexander I" first="Ian" last="Alexander">Ian Alexander</name><affiliation wicri:level="1"><nlm:aff id="JCI31659">The Children’s Hospital at Westmead and Children’s Medical Research Institute, Sydney, New South Wales, Australia.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Children’s Hospital at Westmead and Children’s Medical Research Institute, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Necker–Enfants Malades, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Necker–Enfants Malades, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Von Kalle, Christof" sort="Von Kalle, Christof" uniqKey="Von Kalle C" first="Christof" last="Von Kalle">Christof Von Kalle</name><affiliation><nlm:aff wicri:cut=" and" id="JCI31659">Institute for Molecular Medicine and Cell Research</nlm:aff></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Department of Internal Medicine I, University of Freiburg, Freiburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Internal Medicine I, University of Freiburg, Freiburg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">National Center for Tumor Diseases, Heidelberg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>National Center for Tumor Diseases, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="JCI31659">Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Division of Experimental Hematology, Cincinnati Children’s Research Foundation, Cincinnati, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Cavazzana Calvo, Marina" sort="Cavazzana Calvo, Marina" uniqKey="Cavazzana Calvo M" first="Marina" last="Cavazzana-Calvo">Marina Cavazzana-Calvo</name><affiliation wicri:level="3"><nlm:aff id="JCI31659">INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>INSERM U768, Hôpital Necker, and Faculté de Médecine, Université René Descartes Paris V, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="JCI31659">Département de Biothérapies, Hôpital Necker, Paris, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Département de Biothérapies, Hôpital Necker, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Recent reports have challenged the notion that retroviruses and retroviral vectors integrate randomly into the host genome. These reports pointed to a strong bias toward integration in and near gene coding regions and, for gammaretroviral vectors, around transcription start sites. Here, we report the results obtained from a large-scale mapping of 572 retroviral integration sites (RISs) isolated from cells of 9 patients with X-linked SCID (SCID-X1) treated with a retrovirus-based gene therapy protocol. Our data showed that two-thirds of insertions occurred in or very near to genes, of which more than half were highly expressed in CD34<sup>+</sup> progenitor cells. Strikingly, one-fourth of all integrations were clustered as common integration sites (CISs). The highly significant incidence of CISs in circulating T cells and the nature of their locations indicate that insertion in many gene loci has an influence on cell engraftment, survival, and proliferation. Beyond the observed cases of insertional mutagenesis in 3 patients, these data help to elucidate the relationship between vector insertion and long-term in vivo selection of transduced cells in human patients with SCID-X1.
</p></div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>District de Fribourg-en-Brisgau</li><li>District de Karlsruhe</li><li>Grand Londres</li><li>Hollande-Méridionale</li><li>Massachusetts</li><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Ohio</li><li>Île-de-France</li></region><settlement><li>Fribourg-en-Brisgau</li><li>Heidelberg</li><li>Londres</li><li>Paris</li><li>Rotterdam</li><li>Toulouse</li><li>Évry (Essonne)</li></settlement><orgName><li>University College de Londres</li></orgName></list><tree><noCountry><name sortKey="Hu, Jingqiong" sort="Hu, Jingqiong" uniqKey="Hu J" first="Jingqiong" last="Hu">Jingqiong Hu</name><name sortKey="Prinz, Claudia" sort="Prinz, Claudia" uniqKey="Prinz C" first="Claudia" last="Prinz">Claudia Prinz</name><name sortKey="Siegler, Maria Luise" sort="Siegler, Maria Luise" uniqKey="Siegler M" first="Maria-Luise" last="Siegler">Maria-Luise Siegler</name></noCountry><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Deichmann, Annette" sort="Deichmann, Annette" uniqKey="Deichmann A" first="Annette" last="Deichmann">Annette Deichmann</name></region><name sortKey="Abel, Ulrich" sort="Abel, Ulrich" uniqKey="Abel U" first="Ulrich" last="Abel">Ulrich Abel</name><name sortKey="Abel, Ulrich" sort="Abel, Ulrich" uniqKey="Abel U" first="Ulrich" last="Abel">Ulrich Abel</name><name sortKey="Deichmann, Annette" sort="Deichmann, Annette" uniqKey="Deichmann A" first="Annette" last="Deichmann">Annette Deichmann</name><name sortKey="Glimm, Hanno" sort="Glimm, Hanno" uniqKey="Glimm H" first="Hanno" last="Glimm">Hanno Glimm</name><name sortKey="Schmidt, Manfred" sort="Schmidt, Manfred" uniqKey="Schmidt M" first="Manfred" last="Schmidt">Manfred Schmidt</name><name sortKey="Schmidt, Manfred" sort="Schmidt, Manfred" uniqKey="Schmidt M" first="Manfred" last="Schmidt">Manfred Schmidt</name><name sortKey="Schwarzwaelder, Kerstin" sort="Schwarzwaelder, Kerstin" uniqKey="Schwarzwaelder K" first="Kerstin" last="Schwarzwaelder">Kerstin Schwarzwaelder</name><name sortKey="Schwarzwaelder, Kerstin" sort="Schwarzwaelder, Kerstin" uniqKey="Schwarzwaelder K" first="Kerstin" last="Schwarzwaelder">Kerstin Schwarzwaelder</name><name sortKey="Von Kalle, Christof" sort="Von Kalle, Christof" uniqKey="Von Kalle C" first="Christof" last="Von Kalle">Christof Von Kalle</name><name sortKey="Von Kalle, Christof" sort="Von Kalle, Christof" uniqKey="Von Kalle C" first="Christof" last="Von Kalle">Christof Von Kalle</name><name sortKey="Wissler, Manuela" sort="Wissler, Manuela" uniqKey="Wissler M" first="Manuela" last="Wissler">Manuela Wissler</name></country><country name="France"><region name="Île-de-France"><name sortKey="Hacein Bey Abina, Salima" sort="Hacein Bey Abina, Salima" uniqKey="Hacein Bey Abina S" first="Salima" last="Hacein-Bey-Abina">Salima Hacein-Bey-Abina</name></region><name sortKey="Cavazzana Calvo, Marina" sort="Cavazzana Calvo, Marina" uniqKey="Cavazzana Calvo M" first="Marina" last="Cavazzana-Calvo">Marina Cavazzana-Calvo</name><name sortKey="Cavazzana Calvo, Marina" sort="Cavazzana Calvo, Marina" uniqKey="Cavazzana Calvo M" first="Marina" last="Cavazzana-Calvo">Marina Cavazzana-Calvo</name><name sortKey="Delabesse, Eric" sort="Delabesse, Eric" uniqKey="Delabesse E" first="Eric" last="Delabesse">Eric Delabesse</name><name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name><name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name><name sortKey="Fischer, Nicolas" sort="Fischer, Nicolas" uniqKey="Fischer N" first="Nicolas" last="Fischer">Nicolas Fischer</name><name sortKey="Garrigue, Alexandrine" sort="Garrigue, Alexandrine" uniqKey="Garrigue A" first="Alexandrine" last="Garrigue">Alexandrine Garrigue</name><name sortKey="Gyapay, Gabor" sort="Gyapay, Gabor" uniqKey="Gyapay G" first="Gabor" last="Gyapay">Gabor Gyapay</name><name sortKey="Hacein Bey Abina, Salima" sort="Hacein Bey Abina, Salima" uniqKey="Hacein Bey Abina S" first="Salima" last="Hacein-Bey-Abina">Salima Hacein-Bey-Abina</name><name sortKey="Hue, Christophe" sort="Hue, Christophe" uniqKey="Hue C" first="Christophe" last="Hue">Christophe Hue</name><name sortKey="Hue, Christophe" sort="Hue, Christophe" uniqKey="Hue C" first="Christophe" last="Hue">Christophe Hue</name><name sortKey="Prum, Bernard" sort="Prum, Bernard" uniqKey="Prum B" first="Bernard" last="Prum">Bernard Prum</name><name sortKey="Villeval, Jean Luc" sort="Villeval, Jean Luc" uniqKey="Villeval J" first="Jean-Luc" last="Villeval">Jean-Luc Villeval</name><name sortKey="Weissenbach, Jean" sort="Weissenbach, Jean" uniqKey="Weissenbach J" first="Jean" last="Weissenbach">Jean Weissenbach</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Brugman, Martijn H" sort="Brugman, Martijn H" uniqKey="Brugman M" first="Martijn H." last="Brugman">Martijn H. Brugman</name></region><name sortKey="De Ridder, Dick" sort="De Ridder, Dick" uniqKey="De Ridder D" first="Dick" last="De Ridder">Dick De Ridder</name><name sortKey="De Ridder, Dick" sort="De Ridder, Dick" uniqKey="De Ridder D" first="Dick" last="De Ridder">Dick De Ridder</name><name sortKey="Pike Overzet, Karin" sort="Pike Overzet, Karin" uniqKey="Pike Overzet K" first="Karin" last="Pike-Overzet">Karin Pike-Overzet</name><name sortKey="Staal, Frank J T" sort="Staal, Frank J T" uniqKey="Staal F" first="Frank J. T." last="Staal">Frank J. T. Staal</name><name sortKey="Wagemaker, Gerard" sort="Wagemaker, Gerard" uniqKey="Wagemaker G" first="Gerard" last="Wagemaker">Gerard Wagemaker</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Fraser, Christopher C" sort="Fraser, Christopher C" uniqKey="Fraser C" first="Christopher C." last="Fraser">Christopher C. Fraser</name></region><name sortKey="Aronow, Bruce" sort="Aronow, Bruce" uniqKey="Aronow B" first="Bruce" last="Aronow">Bruce Aronow</name><name sortKey="Klanke, Chuck" sort="Klanke, Chuck" uniqKey="Klanke C" first="Chuck" last="Klanke">Chuck Klanke</name><name sortKey="Von Kalle, Christof" sort="Von Kalle, Christof" uniqKey="Von Kalle C" first="Christof" last="Von Kalle">Christof Von Kalle</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Howe, Steven J" sort="Howe, Steven J" uniqKey="Howe S" first="Steven J." last="Howe">Steven J. Howe</name></region><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J." last="Thrasher">Adrian J. Thrasher</name><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J." last="Thrasher">Adrian J. Thrasher</name></country><country name="Australie"><noRegion><name sortKey="Alexander, Ian" sort="Alexander, Ian" uniqKey="Alexander I" first="Ian" last="Alexander">Ian Alexander</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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