{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:10:54Z","timestamp":1787008254390,"version":"build-2736575974"},"reference-count":45,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"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":[[2025,7]]},"abstract":"<jats:p>Recombinant adeno-associated viruses (AAVs) are clinically relevant vectors for gene therapy that persist largely as extrachromosomal episomes but also infrequently integrate into host genomes. Valoctocogene roxaparvovec is an approved AAV-based gene therapy for severe hemophilia A. We present a molecular characterization of the vector integration profiles in 5 human biopsy samples from valoctocogene roxaparvovec clinical trials as well as in samples from valoctocogene roxaparvovec\u2013treated nonhuman primates (NHPs). The number of genomic integrations was substantially below the previously reported number of transgene-expressing cells, and integration profiles were similar between human and NHP samples. The integration profiles were polyclonal, similarly distributed across the genome, and demonstrated a small bias toward regions of open chromatin and actively transcribed genes, with no relative enrichment in cancer-associated genes. These observations were replicated between species and support the concept that preclinical assessment of AAV vector integration in NHPs is representative of outcomes in humans.<\/jats:p>","DOI":"10.1089\/hum.2024.236","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:14:01Z","timestamp":1749014041000},"page":"945-955","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Recombinant Adeno-Associated Virus Integration Profiles in Nonhuman Primates and Gene Therapy Participants after Treatment with Valoctocogene Roxaparvovec"],"prefix":"10.1177","volume":"36","author":[{"given":"Chris B.","family":"Russell","sequence":"first","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vettermann","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Agarwal","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Witt","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt","family":"Clark","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Arens","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Fronza","sequence":"additional","affiliation":[{"name":"ProtaGene GmbH, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M.","family":"Obrochta Moss","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Kasprzyk","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyen","family":"Tran","sequence":"additional","affiliation":[{"name":"Haemostasis &amp; Thrombosis Unit, Haemophilia Treatment Centre, The Alfred Hospital, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Kenet","sequence":"additional","affiliation":[{"name":"The National Hemophilia Center and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Raheja","sequence":"additional","affiliation":[{"name":"The Royal London Hospital Haemophilia Centre, Barts Health NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Lester","sequence":"additional","affiliation":[{"name":"University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Eggan","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Zoog","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc., Novato, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.72.11.8568-8577.1998"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.75.15.6969-6976.2001"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci79213"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-302729"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1179"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.72.7.5919-5926.1998"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0741-7"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.52"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2013.166"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3230"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.08.031"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007280"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci31659"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci35700"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200301163480314"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088547"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci35798"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1393"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.03.008"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.7326\/m19-1208"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.09.020"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-023-00615-4"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01751-0"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15071"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2023.04.009"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx111"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.11.001"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0060-1"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211075"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2024.102615"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2023.134"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01974-7"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318281"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3389"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2024.04.001"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e318180e47a"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw0726"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1670-9"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03974-6"},{"key":"e_1_3_6_46_2","first-page":"547","volume-title":"Proceedings of the Fourth Berkeley Symposium on Mathematical Statistics and Probability","author":"R\u00e9nyi A","year":"1961","unstructured":"R\u00e9nyi A. On measures of entropy and information. In: Proceedings of the Fourth Berkeley Symposium on Mathematical Statistics and Probability. (Neyman J. ed.) University of California Press: Berkeley, Calif; 1961; pp. 547\u2013561."}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2024.236","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2024.236","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2024.236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:50:40Z","timestamp":1777449040000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2024.236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":45,"journal-issue":{"issue":"13-14","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1089\/hum.2024.236"],"URL":"https:\/\/doi.org\/10.1089\/hum.2024.236","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}