{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:43:04Z","timestamp":1791027784463,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T00:00:00Z","timestamp":1242691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The genomic integration of a lentiviral vector developed for the treatment of Wiskott\u2013Aldrich syndrome (WAS) was assessed by localizing the vector insertion sites (IS) in a murine model of gene therapy for the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transduced hematopoietic progenitor cells were transplanted into mice or cultured <jats:italic>in vitro<\/jats:italic>. The IS were determined in the genomic DNA from blood, the bone marrow of the animals and from cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequencing vector\u2013genomic DNA junctions yielded more than 150 IS of which 50\u201370% were located in transcription units. To obtain additional sequences from the population of cultured cells, we used a vector\u2010tag concatenation technique providing 190 additional IS. Altogether, the profiles confirmed the bias for integration in transcription units. The vector did not congregate as hotspots and did not appear to target specific categories of genes. The diversity of the IS reflected the initial marking of a polyclonal population of cells. However, relatively few vector IS were found <jats:italic>in vivo<\/jats:italic> because only 30\u201340 unique IS were identified in each mouse using this approach. Although four to ten IS were shared by the blood and bone marrow, no common IS was found between mice or between any mouse and the cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken as a whole, the pattern of genomic insertion of the WAS lentiviral vector was diverse and similar to that previously described for other HIV\u20101\u2010derived lentiviral vectors. Testing cells destined for transplantation is unlikely to predict specific IS to be selected <jats:italic>in vivo<\/jats:italic>. Copyright \u00a9 2009 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1346","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T11:06:35Z","timestamp":1242731195000},"page":"645-654","source":"Crossref","is-referenced-by-count":17,"title":["Diverse genomic integration of a lentiviral vector developed for the treatment of Wiskott\u2013Aldrich syndrome"],"prefix":"10.1002","volume":"11","author":[{"given":"Julie","family":"Mantovani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Charrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Eckenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Saurin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Danos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Perea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Galy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,5,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302440"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.17.303"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302863"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.31"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1263"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020234"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-044156"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300159"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl716"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80590-7"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.17.253"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00623-08"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001340"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-068759"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1216"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2009.3"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.1346","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.1346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T21:37:45Z","timestamp":1699911465000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.1346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,19]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2009,8]]}},"alternative-id":["10.1002\/jgm.1346"],"URL":"https:\/\/doi.org\/10.1002\/jgm.1346","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,5,19]]}}}