{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:57:49Z","timestamp":1773727069289,"version":"3.50.1"},"reference-count":142,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Haemophilia therapy has evolved from rudimentary transfusion\u2010based approaches to an unprecedented level of innovation with glimmers of functional cure brought by gene therapy. After decades of misfires, gene therapy has normalized factor (F)VIII and factor (F)IX levels in some individuals in the long term. Several clinical programmes testing adeno\u2010associated viral (AAV) vector gene therapy are approaching completion with imminent regulatory approvals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Phase 3 studies along with multiyear follow\u2010up in earlier phase investigations raised questions about efficacy as well as short\u2010 and long\u2010term safety, prompting a reappraisal of AAV vector gene therapy. Liver toxicities, albeit mostly low\u2010grade, occur in the first year in at least some individuals in all haemophilia A and B trials and are poorly understood. Extreme variability and unpredictability of outcome, as well as a slow decline in factor expression (seemingly unique to FVIII gene therapy), are vexing because immune responses to AAV vectors preclude repeat dosing, which could increase suboptimal or restore declining expression, while overexpression may result in phenotoxicity. The long\u2010term safety will need lifelong monitoring because AAV vectors, contrary to conventional wisdom, integrate into chromosomes at the rate that calls for vigilance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>AAV transduction and transgene expression engage the host immune system, cellular DNA processing, transcription and translation machineries in ways that have been only cursorily studied in the clinic. Delineating those mechanisms will be key to finding mitigants and solutions to the remaining problems, and including individuals who cannot avail of gene therapy at this time.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14530","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T10:07:24Z","timestamp":1651831644000},"page":"35-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene therapy \u2013 are we ready now?"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-1958","authenticated-orcid":false,"given":"Radoslaw","family":"Kaczmarek","sequence":"first","affiliation":[{"name":"Coagulation Products Safety Supply and Access Committee World Federation of Hemophilia  Montreal Quebec Canada"},{"name":"Wells Center for Pediatric Research Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)40031-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01207a034"},{"key":"e_1_2_8_4_1","first-page":"312","article-title":"High potency anti\u2010haemophilic factor prepared from cryoglobulin precipitate","volume":"203","author":"Pool JG","year":"1964","journal-title":"Nat Publ Gr"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2006.11.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.21037\/aob.2018.05.03"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02213.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16311"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/299178a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/312342a0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/312326a0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/312337a0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/312330a0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13221"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.11.006"},{"key":"e_1_2_8_18_1","first-page":"0","article-title":"Laboratory testing in hemophilia: impact of factor and non\u2010factor replacement therapy on coagulation assays","author":"Peyvandi F","year":"2020","journal-title":"J Thromb Haemost"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.03.137"},{"issue":"1","key":"e_1_2_8_20_1","first-page":"1","article-title":"Unsuccessful trial of gene replacement in arginase deficiency","volume":"119","author":"Terheggen HG","year":"1975","journal-title":"Z Kinderheilkd"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.137.4.1091"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.2.438.438"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39116-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1023"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8211118"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.3056"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2353"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.11.4671.bloodjournal87114671"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5804"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/4743"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/4751"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-270"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/4698"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/73387"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106073442301"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0167"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2000.0048"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00926.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14023"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/73464"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3296"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.05.004"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01460.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1549"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316887"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508685103"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-5115"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108046"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-820720"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407309"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-804419"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904377"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.20.12089"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-124091"},{"key":"e_1_2_8_56_1","unstructured":"ChowdaryP ShapiroS MakrisM et al. A Novel Adeno Associated Virus (AAV) Gene Therapy (FLT180a) Achieves Normal FIX Activity Levels in Severe Hemophilia B (HB) Patients (B\u2010AMAZE Study). ISTH 2020 Congress Abstracts."},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000811"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708483"},{"key":"e_1_2_8_60_1","unstructured":"BioMarin Announces Selection of Factor VIII Gene Therapy Drug Development Candidate BMN 270 for the Treatment of Hemophilia A. 1\/13\/2014.https:\/\/investors.biomarin.com\/2014\u201001\u201013\u2010BioMarin\u2010Announces\u2010Selection\u2010of\u2010Factor\u2010VIII\u2010Gene\u2010Therapy\u2010Drug\u2010Development\u2010Candidate\u2010BMN\u2010270\u2010for\u2010the\u2010Treatment\u2010of\u2010Hemophilia\u2010A"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12411"},{"key":"e_1_2_8_62_1","unstructured":"GeorgeL EysterE RagniM et al. Phase I\/II Trial of SPK\u20108011: Stable and Durable FVIII Expression After AAV Gene Transfer for Hemophilia A \u2010 ISTH 2020 Congress Abstracts."},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2104205"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-118256"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139803"},{"key":"e_1_2_8_66_1","first-page":"1","article-title":"The intersection of vector biology, gene therapy, and hemophilia","author":"Lisowski L","year":"2021","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708538"},{"key":"e_1_2_8_68_1","unstructured":"PipeSW LeebeekFW RechtM et al. 52 Week Efficacy and Safety of Etranacogene Dezaparvovec in Adults with Severe or Moderate\u2010severe Hemophilia B: Data from the Phase 3 HOPE\u2010B Gene Therapy Trial \u2010 ISTH 2021 Congress Abstracts."},{"key":"e_1_2_8_69_1","unstructured":"LeebeekFW MiesbachW RechtM et al. Clinical Outcomes in Adults with Hemophilia B with and without Pre\u2010existing Neutralizing Antibodies to AAV5: 6 Month Data from the Phase 3 Etranacogene Dezaparvovec HOPE\u2010B Gene Therapy Trial \u2010 ISTH 2021 Congress Abstracts."},{"key":"e_1_2_8_70_1","unstructured":"OzeloMC MahlanguJ PasiKJ et al. Efficacy and Safety of Valoctocogene Roxaparvovec Adeno\u2010associated Virus Gene Transfer for Severe Hemophilia A: Results from the Phase 3 GENEr8\u20101 Trial \u2010 ISTH 2021 Congress Abstracts."},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2019000007"},{"key":"e_1_2_8_72_1","unstructured":"PasiKJ RangarajanS RobinsonTM et al. Hemostatic Response is Maintained for up to 5 Years Following Treatment with Valoctocogene Roxaparvovec an AAV5\u2010hFVIII\u2010SQ Gene Therapy for Severe Hemophilia A \u2010 ISTH 2021 Congress Abstracts."},{"issue":"2","key":"e_1_2_8_73_1","first-page":"1","article-title":"Journey to the Center of the Cell: tracing the Path of AAV Transduction","volume":"27","author":"Dhungel BP","year":"2020","journal-title":"Trends Mol Med"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13504"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.02.003"},{"issue":"7","key":"e_1_2_8_76_1","first-page":"1096","article-title":"IgG\u2010cleaving endopeptidase enables in vivo gene therapy in the presence of anti\u2010AAV neutralizing antibodies","volume":"26","author":"Leborgne C","year":"2020","journal-title":"Nat Med 2020 267"},{"key":"e_1_2_8_77_1","unstructured":"https:\/\/www.hemophilia.org\/news\/fda\u2010places\u2010the\u2010pfizersangamo\u2010therapeutics\u2010phase\u20103\u2010affine\u2010haemophilia\u2010a\u2010gene\u2010therapy\u2010study\u2010on\u2010clinical\u2010hold"},{"key":"e_1_2_8_78_1","unstructured":"https:\/\/chscontact.ca\/dangerously\u2010high\u2010fix\u2010levels\u2010reported\u2010in\u2010hemophilia\u2010b\u2010gene\u2010therapy"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.01.015"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30035-1"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02539.x"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005260"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.01.001"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009285"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004625"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.01.026"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.07.006"},{"key":"e_1_2_8_88_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2020.00670","article-title":"Human Immune Responses to Adeno\u2010Associated Virus (AAV) Vectors","volume":"11","author":"Ronzitti G","year":"2020","journal-title":"Front Immunol"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.12.010"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.29099.rmk"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202000022"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13525"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.1.426-439.2006"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.3.1949-1955.1999"},{"key":"e_1_2_8_95_1","article-title":"Type I Interferon Sensing by Conventional Dendritic Cells and CD4+ T Help are both Requisite for Cross\u2010priming of AAV Capsid\u2010specific CD8+ T Cells","author":"Shirley JL","year":"2019","journal-title":"Mol Ther"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-751040"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12412"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400666"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502160200"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809677105"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002867"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1612910"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.258"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.6"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00649-08"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.15.6969-6976.2001"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8568-8577.1998"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.280"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3271-9_2"},{"key":"e_1_2_8_110_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2021.658399","article-title":"Anti\u2010AAV Antibodies in AAV Gene Therapy: current Challenges and Possible Solutions","volume":"12","author":"Weber T","year":"2021","journal-title":"Front Immunol"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005683"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008974"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15281"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000405"},{"key":"e_1_2_8_115_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.128683"},{"key":"e_1_2_8_116_1","volume-title":"Long Term Safety and Efficacy of Adeno\u2010associated Viral Gene Therapy in a Canine Hemophilia A Model","author":"Batty P","year":"2019"},{"key":"e_1_2_8_117_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13605"},{"key":"e_1_2_8_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0741-7"},{"key":"e_1_2_8_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00756-9"},{"key":"e_1_2_8_120_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13489"},{"key":"e_1_2_8_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.10.025"},{"key":"e_1_2_8_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.10.018"},{"key":"e_1_2_8_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.08.031"},{"key":"e_1_2_8_124_1","first-page":"1","article-title":"The critical need for postmarketing surveillance in gene therapy for haemophilia","author":"Konkle BA","year":"2020","journal-title":"Haemophilia"},{"key":"e_1_2_8_125_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15023"},{"key":"e_1_2_8_126_1","unstructured":"Liver Safety Case Report from the Phase 3 HOPE\u2010B Gene Therapy Trial in Adults with Hemophilia B \u2010 ISTH Congress Abstracts."},{"key":"e_1_2_8_127_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba9188"},{"key":"e_1_2_8_128_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2005056"},{"key":"e_1_2_8_129_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002142"},{"key":"e_1_2_8_130_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.10.005"},{"key":"e_1_2_8_131_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14131"},{"key":"e_1_2_8_132_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13673"},{"key":"e_1_2_8_133_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13971"},{"key":"e_1_2_8_134_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012129"},{"key":"e_1_2_8_135_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010864"},{"key":"e_1_2_8_136_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14012"},{"key":"e_1_2_8_137_1","first-page":"1","article-title":"Evolution of haemophilia integrated care in the era of gene therapy: treatment centre's readiness in United States and EU","author":"Miesbach W","year":"2021","journal-title":"Haemophilia"},{"key":"e_1_2_8_138_1","article-title":"How to discuss gene therapy for haemophilia? A patient and physician perspective","volume":"13769","author":"Miesbach W","year":"2019","journal-title":"Haemophilia"},{"key":"e_1_2_8_139_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100759"},{"key":"e_1_2_8_140_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14027"},{"key":"e_1_2_8_141_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-021-00017-7"},{"key":"e_1_2_8_142_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_2_8_143_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00487-6"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14530","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.14530","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14530","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:44:40Z","timestamp":1698846280000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5]]},"references-count":142,"journal-issue":{"issue":"S4","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/hae.14530"],"URL":"https:\/\/doi.org\/10.1111\/hae.14530","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5]]},"assertion":[{"value":"2021-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}