{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:26:26Z","timestamp":1771046786900,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Attempts to achieve a functional cure or amelioration of the severe X linked bleeding disorders haemophilia A (factor VIII deficiency) and haemophilia B (factor IX deficiency) using AAV\u2010based vectors have been frustrated by immune responses that limit efficacy and durability. The immune responses include adaptive and innate pathways as well as cytokine mediated inflammation, especially of the target organ cells\u2014hepatocytes. Immune suppression has only been partly effective in clinical trials at ameliorating the immune response and the lack of good animal models has delayed progress in identifying mechanisms and developing more effective approaches to controlling these effects of AAV gene transfer. Here we discuss the arguments for and against more potent immunosuppression to improve factor expression after AAV\u2010mediated gene therapy.<\/jats:p>","DOI":"10.1111\/jvh.13934","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:44:21Z","timestamp":1712925861000},"page":"21-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The complex, confusing and poorly understood immune responses to <scp>AAV<\/scp>\u2010mediated gene transfer in haemophilia\u2014Is more or less immunosuppression required?"],"prefix":"10.1111","volume":"31","author":[{"given":"Edward G. D.","family":"Tuddenham","sequence":"first","affiliation":[{"name":"University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham R.","family":"Foster","sequence":"additional","affiliation":[{"name":"Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108046"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407309"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211075"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211644"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01751-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.08.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.01.026"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-314518"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809677105"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.07.005"},{"key":"e_1_2_8_14_1","first-page":"00869\u20103","article-title":"Deciphering conundrums of adeno\u2010associated virus liver\u2010directed gene therapy: focus on hemophilia","volume":"1538","author":"Pierce GF","year":"2023","journal-title":"J Thromb Haemost"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T12:44:25Z","timestamp":1712925865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":13,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/jvh.13934"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13934","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2024-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}