{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:04:14Z","timestamp":1789668254362,"version":"4.0.1"},"reference-count":62,"publisher":"SAGE Publications","issue":"1-2","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"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":[[2021,1]]},"abstract":"<jats:p>\n                    Hematopoietic stem and progenitor cell (HSPC)-based\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene therapy has demonstrated clinical success for X-linked severe combined immunodeficiency (SCID-X1) patients who lack a suitable donor for HSPC transplantation. Nevertheless, this form of treatment is associated with an increased risk of infectious disease complications and genotoxicity mainly due to the conditioning regimen. In addition,\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene therapy approaches require sophisticated facilities to manufacture gene-modified cells and to care for the patients after chemotherapy. Considering these impediments, we have developed an\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    gene therapy approach to treat canine SCID-X1 after HSPC mobilization and systemic delivery of the therapeutic vector. Here, we investigated the use of the cocal envelope to pseudotype a lentiviral (LV) vector expressing a functional gammaC gene. The cocal envelope is resistant to serum inactivation compared with the commonly used vesicular stomatitis virus envelope glycoprotein (VSV-G) envelope and thus well suited for systemic delivery. Two SCID-X1 neonatal canines treated with this approach achieved long-term therapeutic immune reconstitution with no prior conditioning. Therapeutic levels of gene-corrected CD3\n                    <jats:sup>+<\/jats:sup>\n                    T cells were demonstrated for at least 16 months, and all other correlates of T cell functionality were within normal range. Retroviral integration-site analysis demonstrated polyclonal T cell reconstitution. Comparative analysis of integration profiles of foamy viral (FV) vector and cocal LV vector after\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    gene therapy found distinct integration-site patterns. These data demonstrate that clinically relevant and durable correction of canine SCID-X1 can be achieved with\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    delivery of cocal LV. Since manufacturing of cocal LV is similar to VSV-G LV, this approach is easily translatable to a clinical setting, thus providing for a highly portable and accessible gene therapy platform for SCID-X1.\n                  <\/jats:p>","DOI":"10.1089\/hum.2020.127","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T03:24:46Z","timestamp":1596252286000},"page":"113-127","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["<i>In Vivo<\/i>\n                    Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector"],"prefix":"10.1177","volume":"32","author":[{"given":"Yogendra S.","family":"Rajawat","sequence":"first","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Humbert","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah M.","family":"Cook","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Radtke","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dnyanada","family":"Pande","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Enstrom","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Wohlfahrt","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Kiem","sequence":"additional","affiliation":[{"name":"Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA."},{"name":"Pathology, University of Washington School of Medicine, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90167-O"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.028"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104614"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.005"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815408"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401177"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.43"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad8856"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00443"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705342"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.13.4185"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1000164"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-538926"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016451"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2015.004"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2012.25"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.70"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2007.05.013"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13880-1"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-1133-2_22"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt593"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1113"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229202"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3290"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0653-6"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1015"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.009"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11121091"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.282"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2014.01.001"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-05-1937"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02293-5"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah6506"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.48"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2988"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2414"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-41020-40150-z"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-115022"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11400"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2000.0116"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.11.004"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.01.001"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2015.08.003"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.4.1206.h8001206_1206_1214"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1997.8.17-2079"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-558163"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017007773"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(00)00193-8"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5420"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214441110"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.5.2936-2945.2003"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.1.38.bloodjournal85138"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00065"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-362533"},{"key":"e_1_3_7_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.047"},{"key":"e_1_3_7_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09328"},{"key":"e_1_3_7_58_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2007.011"},{"key":"e_1_3_7_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510046103"},{"key":"e_1_3_7_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.03.021"},{"key":"e_1_3_7_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.78"},{"key":"e_1_3_7_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.02.001"},{"key":"e_1_3_7_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0550-z"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2020.127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2020.127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2020.127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:55:36Z","timestamp":1777449336000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2020.127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":62,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1089\/hum.2020.127"],"URL":"https:\/\/doi.org\/10.1089\/hum.2020.127","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}