{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:50:14Z","timestamp":1792817414302,"version":"4.5.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>\n                    Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the\n                    <jats:italic toggle=\"yes\">ITGB2<\/jats:italic>\n                    gene and is characterized by recurrent and life-threatening bacterial infections. These mutations lead to defective or absent expression of \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    integrins on the leukocyte surface, compromising adhesion and extravasation at sites of infection. Three different lentiviral vectors (LVs) conferring ubiquitous or preferential expression of CD18 in myeloid cells were constructed and tested in human and mouse LAD-I cells. All three hCD18-LVs restored CD18 and CD11a membrane expression in LAD-I patient-derived lymphoblastoid cells. Corrected cells recovered the ability to aggregate and bind to sICAM-1 after stimulation. All vectors induced stable hCD18 expression in hematopoietic cells from mice with a hypomorphic\n                    <jats:italic toggle=\"yes\">Itgb2<\/jats:italic>\n                    mutation (CD18\n                    <jats:sup>HYP<\/jats:sup>\n                    ), both\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    after transplantation of corrected cells into primary and secondary CD18\n                    <jats:sup>HYP<\/jats:sup>\n                    recipients. hCD18\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic cells from transplanted CD18\n                    <jats:sup>HYP<\/jats:sup>\n                    mice also showed restoration of mCD11a surface co-expression. The analysis of\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    neutrophil migration in CD18\n                    <jats:sup>HYP<\/jats:sup>\n                    mice subjected to two different inflammation models demonstrated that the LV-mediated gene therapy completely restored neutrophil extravasation in response to inflammatory stimuli. Finally, these vectors were able to correct the phenotype of human myeloid cells derived from CD34\n                    <jats:sup>+<\/jats:sup>\n                    progenitors defective in ITGB2 expression. These results support for the first time the use of hCD18-LVs for the treatment of LAD-I patients in clinical trials.\n                  <\/jats:p>","DOI":"10.1089\/hum.2016.016","type":"journal-article","created":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T13:35:57Z","timestamp":1460122557000},"page":"668-678","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Lentiviral Vector-Mediated Correction of a Mouse Model of Leukocyte Adhesion Deficiency Type I"],"prefix":"10.1177","volume":"27","author":[{"given":"Diego","family":"Leon-Rico","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Aldea","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Sanchez-Baltasar","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mesa-Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Record","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan O.","family":"Burns","sequence":"additional","affiliation":[{"name":"Royal Free London NHS Foundation Trust","place":["United Kingdom"]},{"name":"University College London Institute of Immunity and Transplantation","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Santilli","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"University College London Institute of Child Health","place":["United Kingdom"]},{"name":"Great Ormond Street Hospital Foundation Trust NHS Trust","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Bueren","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Almarza","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT)","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.38.020187.001135"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90215-7"},{"key":"e_1_3_3_4_2","first-page":"963","article-title":"Leucocyte adhesion deficiency-1","volume":"39","author":"Simon A","year":"2002","unstructured":"Simon A, , Pillai S, , Raghupathy P, et al. Leucocyte adhesion deficiency-1. Indian Pediatr, 2002; 39:963\u2013966.","journal-title":"Indian Pediatr"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.07.005"},{"key":"e_1_3_3_6_2","first-page":"16","article-title":"Lessons from rare maladies: Leukocyte adhesion deficiency syndromes","volume":"20","author":"Harris ES","year":"2013","unstructured":"Harris ES, , Weyrich AS, , Zimmerman GA. Lessons from rare maladies: Leukocyte adhesion deficiency syndromes. Curr Opin Hematol, 2013; 20:16\u201325.","journal-title":"Curr Opin Hematol"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)61142-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.6.2379.bloodjournal8662379"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1991.2.3-221"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1972597"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1993.4.1-25"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.50.2.168"},{"key":"e_1_3_3_13_2","first-page":"383","article-title":"Gene therapy for leukocyte adhesion deficiency","volume":"2","author":"Bauer TR","year":"2000","unstructured":"Bauer TRJr., , Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther, 2000; 2:383\u2013388.","journal-title":"Curr Opin Mol Ther"},{"key":"e_1_3_3_14_2","first-page":"1622","article-title":"Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: An animal model","volume":"69","author":"Giger U","year":"1987","unstructured":"Giger U, , Boxer LA, , Simpson PJ, et al. Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: An animal model. Blood, 1987; 69:1622\u20131630.","journal-title":"Blood"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2460\/javma.1975.166.05.443"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1695"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2010.130"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1227"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.203"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28873"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.141"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233158"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-060814"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.08.006"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.11.024"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1316"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.132"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.226"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.3.1571"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1762"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20110101"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.12.714"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2011.140"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1191"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.4.1629.bloodjournal8641629"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.03.098"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2985"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2013.21"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013-0206"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.179"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115448"},{"key":"e_1_3_3_42_2","first-page":"A111","article-title":"Efficacy of a gene therapy approach using a humanized model of Fanconi anemia","volume":"23","author":"Banos R","year":"2012","unstructured":"Banos R, , Valeri A, , Alvarez L, et al. Efficacy of a gene therapy approach using a humanized model of Fanconi anemia. Hum Gene Ther, 2012; 23:A111.","journal-title":"Hum Gene Ther"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2014.37"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2016.016","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2016.016","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2016.016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:02:42Z","timestamp":1779692562000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2016.016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1089\/hum.2016.016"],"URL":"https:\/\/doi.org\/10.1089\/hum.2016.016","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]}}}