{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:00:39Z","timestamp":1789012839607,"version":"build-2803163510"},"reference-count":183,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Blood Reviews"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1016\/j.blre.2022.101011","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T09:00:18Z","timestamp":1661245218000},"page":"101011","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Progress, and prospects in the therapeutic armamentarium of persons with congenital hemophilia. Defining the place for liver-directed gene therapy"],"prefix":"10.1016","volume":"58","author":[{"given":"Giovanni","family":"Di Minno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimondo","family":"De Cristofaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Brunetti-Pierri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Pastore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Castaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Trama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Di Minno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.blre.2022.101011_bb0005","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1055\/s-0037-1615621","article-title":"Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the international society on thrombosis and Haemostasis","volume":"85","author":"White","year":"2001","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0010","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1056\/NEJM200106073442307","article-title":"The hemophilias--from royal genes to gene therapy","volume":"344","author":"Mannucci","year":"2001","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0015","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/hae.13816","article-title":"Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia","volume":"25","author":"Peyvandi","year":"2019","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/hematology.2019000007","article-title":"Gene therapy for hemophilia","volume":"2019","author":"Nathwani","year":"2019","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"10.1016\/j.blre.2022.101011_bb0025","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines7030061","article-title":"Perspective on adenoviruses: epidemiology, pathogenicity, and gene therapy","volume":"7","author":"Crenshaw","year":"2019","journal-title":"Biomedicines."},{"key":"10.1016\/j.blre.2022.101011_bb0030","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1182\/blood-2017-08-742312","article-title":"Novel approaches to hemophilia therapy: successes and challenges","volume":"130","author":"Arruda","year":"2017","journal-title":"Blood."},{"issue":"Suppl. 1","key":"10.1016\/j.blre.2022.101011_bb0035","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1538-7836.2011.04369.x","article-title":"Gene therapy for haemophilia: a long and winding road","volume":"9","author":"High","year":"2011","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0040","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1182\/asheducation-2017.1.587","article-title":"Hemophilia gene therapy comes of age","volume":"2017","author":"George","year":"2017","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"10.1016\/j.blre.2022.101011_bb0045","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ymthe.2020.12.007","article-title":"Current clinical applications of in vivo gene therapy with AAVs","volume":"29","author":"Mendell","year":"2021","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0050","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000540","article-title":"Hemophilia gene therapy: approaching the first licensed product","volume":"5","author":"Batty","year":"2021","journal-title":"HemaSphere."},{"key":"10.1016\/j.blre.2022.101011_bb0055","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1182\/blood-2018-01-824144","article-title":"Hemophilia gene therapy is effective and safe","volume":"131","author":"Makris","year":"2018","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0060","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1080\/14712598.2019.1626370","article-title":"Emicizumab for the prevention of bleeds in hemophilia a","volume":"19","author":"Mahlangu","year":"2019","journal-title":"Expert Opin Biol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0065","doi-asserted-by":"crossref","DOI":"10.1002\/rth2.12567","article-title":"Living with a \"hemophilia-free mind\" - the new ambition of hemophilia care?","volume":"5","author":"Krumb","year":"2021","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0070","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/hae.14309","article-title":"Evolution of haemophilia integrated care in the era of gene therapy: treatment centre's readiness in United States and EU","volume":"27","author":"Miesbach","year":"2021","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0075","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/299178a0","article-title":"Molecular cloning of the gene for human anti-haemophilic factor IX","volume":"299","author":"Choo","year":"1982","journal-title":"Nature."},{"key":"10.1016\/j.blre.2022.101011_bb0080","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1056\/NEJMoa1708538","article-title":"Hemophilia B gene therapy with a high-specific-activity factor IX variant","volume":"377","author":"George","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0085","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1432-1033.1995.tb20776.x","article-title":"Novel forms of B-domain-deleted recombinant factor VIII molecules. Construction and biochemical characterization","volume":"232","author":"Lind","year":"1995","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.blre.2022.101011_bb0090","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gendis.2017.04.001","article-title":"Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine","volume":"4","author":"Lee","year":"2017","journal-title":"Gene Dis"},{"key":"10.1016\/j.blre.2022.101011_bb0095","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1182\/blood-2012-10-462200","article-title":"Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant","volume":"121","author":"McIntosh","year":"2013","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0100","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.89371","article-title":"Circumventing furin enhances factor VIII biological activity and ameliorates bleeding phenotypes in hemophilia models","volume":"1","author":"Siner","year":"2016","journal-title":"JCI Insight"},{"key":"10.1016\/j.blre.2022.101011_bb0105","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1093\/aje\/kwm030","article-title":"Reconstruction of the hepatitis C virus epidemic in the US hemophilia population, 1940-1990","volume":"165","author":"Goedert","year":"2007","journal-title":"Am J Epidemiol"},{"key":"10.1016\/j.blre.2022.101011_bb0110","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.antiviral.2011.10.022","article-title":"Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection","volume":"93","author":"Svicher","year":"2012","journal-title":"Antiviral Res"},{"key":"10.1016\/j.blre.2022.101011_bb0115","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1365-2141.2010.08263.x","article-title":"Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence-based approaches","volume":"150","author":"Coppola","year":"2010","journal-title":"Br J Haematol"},{"key":"10.1016\/j.blre.2022.101011_bb0120","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1182\/blood-2008-06-160432","article-title":"How we treat a hemophilia a patient with a factor VIII inhibitor","volume":"113","author":"Kempton","year":"2009","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0125","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s12185-009-0435-x","article-title":"Evolution of recombinant factor VIII safety: KOGENATE and Kogenate FS\/Bayer","volume":"90","author":"Lusher","year":"2009","journal-title":"Int J Hematol"},{"key":"10.1016\/j.blre.2022.101011_bb0130","first-page":"25","article-title":"Final analysis from the pivotal phase 3 HOPE-B gene therapy trial: stable steady-state efficacy and safety of Etranacogene Dezaparvovec in adults with severe or moderately severe hemophilia B","volume":"28","author":"Miesbach","year":"2022","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0135","series-title":"15th annual congress of European Association for Haemophilia and allied disorders 2022, 2\u20134 February 2022, Virtual Meeting","article-title":"Multiple-year durability data from a phase 2B trial of gene therapy with Etranacogene Dezaparvovec in patients with hemophilia B","author":"Gomez","year":"2022"},{"key":"10.1016\/j.blre.2022.101011_bb0140","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1089\/hum.2014.2540","article-title":"Our journey to successful gene therapy for hemophilia B","volume":"25","author":"Nathwani","year":"2014","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0145","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1182\/blood-2011-09-382317","article-title":"Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer","volume":"119","author":"Buchlis","year":"2012","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0150","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ymthe.2006.05.004","article-title":"Evidence of multiyear factor IX expression by AAV-mediated gene transfer to skeletal muscle in an individual with severe hemophilia B","volume":"14","author":"Jiang","year":"2006","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0155","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1089\/hum.2017.167","article-title":"Advances in gene therapy for hemophilia","volume":"28","author":"Nathwani","year":"2017","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0160","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa1407309","article-title":"Long-term safety and efficacy of factor IX gene therapy in hemophilia B","volume":"371","author":"Nathwani","year":"2014","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0165","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1182\/blood-2017-09-804419","article-title":"Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B","volume":"131","author":"Miesbach","year":"2018","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0170","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1056\/NEJMoa1708483","article-title":"AAV5-factor VIII gene transfer in severe hemophilia a","volume":"377","author":"Rangarajan","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0175","article-title":"Phase I\/II trial of SPK-8011: stable and durable FVIII expression for >2 years with significant ABR improvements in initial dose cohorts following AAV-mediated FVIII gene transfer for hemophilia A [abstract]","volume":"4","author":"George","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0180","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/mt.2010.240","article-title":"Efficacy and safety of long-term prophylaxis in severe hemophilia a dogs following liver gene therapy using AAV vectors","volume":"19","author":"Sabatino","year":"2011","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0185","series-title":"World Federation of Hemophilia Virtual Summit Update. Firstin- human four-year follow-up study of durable therapeutic efficacy and safety: AAV gene therapy with Valoctocogene Roxaparvovec for severe hemophilia A","author":"BioMarin","year":"2020"},{"key":"10.1016\/j.blre.2022.101011_bb0190","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa1908490","article-title":"Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia a","volume":"382","author":"Pasi","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0195","series-title":"BioMarin announces stable and durable annualized bleed control in the largest phase 3 gene therapy study in adults with severe hemophilia A; 134-participant study met all primary and secondary efficacy endpoints at two year analysis","author":"Inc. BP","year":"2022"},{"key":"10.1016\/j.blre.2022.101011_bb0200","series-title":"Hemostatic results for up to 6 years following treatment with valoctocogene roxaparvovec, an AAV5-hFVIII-SQ gene therapy for severe hemophilia A international society on thrombosis and Haemostasis (ISTH) congress. London, United Kingdom","author":"Laffan","year":"2022"},{"key":"10.1016\/j.blre.2022.101011_bb0205","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/hae.14391","article-title":"Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A","volume":"27","author":"Pasi","year":"2021","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0210","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJMoa2113708","article-title":"Valoctocogene Roxaparvovec gene therapy for hemophilia A","volume":"386","author":"Ozelo","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2020.100759","article-title":"Discussing investigational AAV gene therapy with hemophilia patients: a guide","volume":"47","author":"Sidonio","year":"2021","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0220","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1182\/blood-2008-07-167510","article-title":"AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells","volume":"114","author":"Mingozzi","year":"2009","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0225","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1182\/blood-2003-10-3591","article-title":"Bioengineering of coagulation factor VIII for improved secretion","volume":"103","author":"Miao","year":"2004","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0230","doi-asserted-by":"crossref","first-page":"16064","DOI":"10.1038\/mtm.2016.64","article-title":"Overexpression of factor VIII after AAV delivery is transiently associated with cellular stress in hemophilia a mice","volume":"3","author":"Lange","year":"2016","journal-title":"Mol Ther Method Clin Dev"},{"key":"10.1016\/j.blre.2022.101011_bb0235","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1182\/bloodadvances.2018020552","article-title":"The frequency of joint hemorrhages and procedures in nonsevere hemophilia a vs B","volume":"2","author":"Soucie","year":"2018","journal-title":"Blood Adv"},{"key":"10.1016\/j.blre.2022.101011_bb0240","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1182\/blood-2014-02-554501","article-title":"Murine coagulation factor VIII is synthesized in endothelial cells","volume":"123","author":"Everett","year":"2014","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0245","doi-asserted-by":"crossref","first-page":"6461","DOI":"10.1073\/pnas.79.21.6461","article-title":"Isolation and characterization of a cDNA coding for human factor IX","volume":"79","author":"Kurachi","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.blre.2022.101011_bb0250","doi-asserted-by":"crossref","first-page":"5364","DOI":"10.1182\/blood-2009-02-206979","article-title":"Extrahepatic factor VIII production in transplant recipient of hemophilia donor liver","volume":"113","author":"Madeira","year":"2009","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0255","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/jth.12412","article-title":"Human liver sinusoidal endothelial cells but not hepatocytes contain factor VIII","volume":"12","author":"Shahani","year":"2014","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0260","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0140740","article-title":"Factor VIII is synthesized in human endothelial cells, packaged in Weibel-Palade bodies and secreted bound to ULVWF strings","volume":"10","author":"Turner","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.blre.2022.101011_bb0265","doi-asserted-by":"crossref","DOI":"10.1002\/rth2.12654","article-title":"Thrombin generation measured on ST Genesia, a new platform in the coagulation routine lab: assessment of analytical and between-subject variation","volume":"6","author":"Kristensen","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0270","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/jth.15640","article-title":"Thrombin generation for monitoring hemostatic therapy in hemophilia a: a narrative review","volume":"20","author":"Verhagen","year":"2022","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0275","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1373\/clinchem.2015.248625","article-title":"Thrombin generation assay and its application in the clinical laboratory","volume":"62","author":"Tripodi","year":"2016","journal-title":"Clin Chem"},{"key":"10.1016\/j.blre.2022.101011_bb0280","series-title":"Laboratory evaluation of extendend-half-life recombinant FVIII products (EHL-FVIIIs): One stage coagulation assay or chromogenic assay? International society on thrombosis and Haemostasis (ISTH) congress. London, United Kingdom","author":"De Cristofaro","year":"2022"},{"key":"10.1016\/j.blre.2022.101011_bb0285","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2021.100849","article-title":"Perspective - the case for zero bleeds and drug bioequivalence in the treatment of congenital hemophilia A in 2021","volume":"50","author":"Di Minno","year":"2021","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0290","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1055\/s-2008-1066024","article-title":"The phenotypic heterogeneity of severe hemophilia","volume":"34","author":"Jayandharan","year":"2008","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.blre.2022.101011_bb0295","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1055\/s-0034-1395349","article-title":"Phenotypic heterogeneity of hemostasis in severe hemophilia","volume":"41","author":"Nogami","year":"2015","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.blre.2022.101011_bb0300","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.omtm.2019.08.015","article-title":"Clinical considerations for capsid choice in the development of liver-targeted AAV-based gene transfer","volume":"15","author":"Pipe","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.blre.2022.101011_bb0305","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nm1358","article-title":"Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response","volume":"12","author":"Manno","year":"2006","journal-title":"Nat Med"},{"key":"10.1016\/j.blre.2022.101011_bb0310","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/hum.2009.182","article-title":"Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors","volume":"21","author":"Boutin","year":"2010","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0315","doi-asserted-by":"crossref","DOI":"10.1089\/hum.2021.287","article-title":"Global seroprevalence of pre-existing immunity against AAV5 and other AAV serotypes in people with hemophilia A","author":"Klamroth","year":"2022","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0320","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.omtm.2021.05.012","article-title":"Monitoring cell-mediated immune responses in AAV gene therapy clinical trials using a validated IFN-gamma ELISpot method","volume":"22","author":"Patton","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.blre.2022.101011_bb0325","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrg3742","article-title":"Engineering adeno-associated viruses for clinical gene therapy","volume":"15","author":"Kotterman","year":"2014","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.blre.2022.101011_bb0330","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-61779-370-7_11","article-title":"Measuring immune responses to recombinant AAV gene transfer","volume":"807","author":"Martino","year":"2011","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.blre.2022.101011_bb0335","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/2040620718791933","article-title":"Gene therapy for hemophilia: what does the future hold?","volume":"9","author":"Doshi","year":"2018","journal-title":"Ther Adv Hematol"},{"key":"10.1016\/j.blre.2022.101011_bb0340","doi-asserted-by":"crossref","first-page":"R42","DOI":"10.1093\/hmg\/ddv451","article-title":"Progress and challenges in viral vector manufacturing","volume":"25","author":"van der Loo","year":"2016","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.blre.2022.101011_bb0345","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1089\/hum.2016.172","article-title":"Impact of AAV capsid-specific T-cell responses on design and outcome of clinical gene transfer trials with recombinant adeno-associated viral vectors: an evolving controversy","volume":"28","author":"Ertl","year":"2017","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0350","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1056\/NEJMoa0904377","article-title":"X-linked thrombophilia with a mutant factor IX (factor IX Padua)","volume":"361","author":"Simioni","year":"2009","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0355","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1182\/blood-2014-07-588194","article-title":"AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice","volume":"125","author":"Crudele","year":"2015","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0360","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1056\/NEJMoa2119913","article-title":"Phase 1-2 trial of AAVS3 gene therapy in patients with hemophilia B","volume":"387","author":"Chowdary","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0365","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3324\/haematol.2016.156000","article-title":"Tailoring of medical treatment: hemostasis and thrombosis towards precision medicine","volume":"102","author":"Di Minno","year":"2017","journal-title":"Haematologica."},{"key":"10.1016\/j.blre.2022.101011_bb0370","article-title":"Toward more comprehensive homologous recombination deficiency assays in ovarian cancer part 2: medical perspectives","volume":"14","author":"Quesada","year":"2022","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.blre.2022.101011_bb0375","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/j.ymthe.2020.06.001","article-title":"Long-term follow-up of the first in human intravascular delivery of AAV for gene transfer: AAV2-hFIX16 for severe hemophilia B","volume":"28","author":"George","year":"2020","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0380","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1142658","article-title":"AAV vector integration sites in mouse hepatocellular carcinoma","volume":"317","author":"Donsante","year":"2007","journal-title":"Science."},{"key":"10.1016\/j.blre.2022.101011_bb0385","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI79213","article-title":"Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy","volume":"125","author":"Chandler","year":"2015","journal-title":"J Clin Invest"},{"key":"10.1016\/j.blre.2022.101011_bb0390","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/oxfordjournals.jbchem.a002971","article-title":"Identification of a new imprinted gene, Rian, on mouse chromosome 12 by fluorescent differential display screening","volume":"130","author":"Hatada","year":"2001","journal-title":"J Biochem"},{"key":"10.1016\/j.blre.2022.101011_bb0395","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/mt.2016.17","article-title":"Genotoxicity in mice following AAV gene delivery: a safety concern for human gene therapy?","volume":"24","author":"Chandler","year":"2016","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0400","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/gutjnl-2019-318281","article-title":"Adeno-associated virus in the liver: natural history and consequences in tumour development","volume":"69","author":"La Bella","year":"2020","journal-title":"Gut."},{"key":"10.1016\/j.blre.2022.101011_bb0405","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/ng.3389","article-title":"Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas","volume":"47","author":"Nault","year":"2015","journal-title":"Nat Genet"},{"key":"10.1016\/j.blre.2022.101011_bb0410","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2020.100737","article-title":"The evolving landscape of gene therapy for congenital haemophilia: an unprecedented, problematic but promising opportunity for worldwide clinical studies","volume":"46","author":"Spadarella","year":"2021","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0415","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.ymthe.2021.08.031","article-title":"AAV integration in human hepatocytes","volume":"29","author":"Dalwadi","year":"2021","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0420","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/ng1179","article-title":"AAV serotype 2 vectors preferentially integrate into active genes in mice","volume":"34","author":"Nakai","year":"2003","journal-title":"Nat Genet"},{"key":"10.1016\/j.blre.2022.101011_bb0425","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41587-020-0741-7","article-title":"A long-term study of AAV gene therapy in dogs with hemophilia a identifies clonal expansions of transduced liver cells","volume":"39","author":"Nguyen","year":"2021","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.blre.2022.101011_bb0430","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/ng.3893","article-title":"Identification of liver-specific enhancer-promoter activity in the 3\u2032 untranslated region of the wild-type AAV2 genome","volume":"49","author":"Logan","year":"2017","journal-title":"Nat Genet"},{"key":"10.1016\/j.blre.2022.101011_bb0435","doi-asserted-by":"crossref","first-page":"30706","DOI":"10.1074\/jbc.M111.229831","article-title":"DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival","volume":"286","author":"Luk","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1016\/j.blre.2022.101011_bb0440","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2016.06.015","article-title":"Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals","volume":"65","author":"Conti","year":"2016","journal-title":"J Hepatol"},{"key":"10.1016\/j.blre.2022.101011_bb0445","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrgastro.2016.140","article-title":"Liver cancer: effect of HCV clearance with direct-acting antiviral agents on HCC","volume":"13","author":"Llovet","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.blre.2022.101011_bb0450","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000012551","article-title":"The elevated prevalence of risk factors for chronic liver disease among ageing people with hemophilia and implications for treatment","volume":"97","author":"Qvigstad","year":"2018","journal-title":"Medicine."},{"key":"10.1016\/j.blre.2022.101011_bb0455","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.blre.2015.07.004","article-title":"Current concepts in the prevention of pathogen transmission via blood\/plasma-derived products for bleeding disorders","volume":"30","author":"Di Minno","year":"2016","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0460","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1002\/jmv.23818","article-title":"The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals","volume":"86","author":"Mimuro","year":"2014","journal-title":"J Med Virol"},{"key":"10.1016\/j.blre.2022.101011_bb0465","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2174\/156652311796150354","article-title":"Immune responses to AAV in clinical trials","volume":"11","author":"Mingozzi","year":"2011","journal-title":"Curr Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0470","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10112471","article-title":"Emerging immunogenicity and genotoxicity considerations of adeno-associated virus vector gene therapy for hemophilia","volume":"10","author":"Monahan","year":"2021","journal-title":"J Clin Med"},{"key":"10.1016\/j.blre.2022.101011_bb0475","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1038\/mt.2011.108","article-title":"A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8","volume":"19","author":"Monteilhet","year":"2011","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0480","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1479-5876-10-122","article-title":"Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates","volume":"10","author":"Unzu","year":"2012","journal-title":"J Transl Med"},{"key":"10.1016\/j.blre.2022.101011_bb0485","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1038\/s41467-018-06621-3","article-title":"Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration","volume":"9","author":"Meliani","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.blre.2022.101011_bb0490","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1182\/blood-2013-01-306647","article-title":"Immune responses to AAV vectors: overcoming barriers to successful gene therapy","volume":"122","author":"Mingozzi","year":"2013","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0495","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-020-0911-7","article-title":"IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies","volume":"26","author":"Leborgne","year":"2020","journal-title":"Nat Med"},{"key":"10.1016\/j.blre.2022.101011_bb0500","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.omtm.2019.05.009","article-title":"Therapeutic hFIX activity achieved after single AAV5-hFIX treatment in hemophilia B patients and NHPs with pre-existing anti-AAV5 NABs","volume":"14","author":"Majowicz","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.blre.2022.101011_bb0505","article-title":"Hyperactivity of factor IX Padua (R338L) depends on factor VIIIa cofactor activity","volume":"5","author":"Samelson-Jones","year":"2019","journal-title":"JCI Insight"},{"key":"10.1016\/j.blre.2022.101011_bb0510","article-title":"A novel adeno associated virus (AAV) gene therapy (FLT180a) achieves normal FIX activity levels in severe hemophilia B (HB) patients (B-AMAZE study) [abstract]","volume":"4","author":"Chowdary","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0515","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/jth.14343","article-title":"High levels of coagulation factors and venous thrombosis risk: strongest association for factor VIII and von Willebrand factor","volume":"17","author":"Rietveld","year":"2019","journal-title":"J Thromb Haemostasis"},{"key":"10.1016\/j.blre.2022.101011_bb0520","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1182\/blood-2009-07-215665","article-title":"How I treat age-related morbidities in elderly persons with hemophilia","volume":"114","author":"Mannucci","year":"2009","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0525","series-title":"Therapeutics report severe adverse event (SAE) from phase 3 AFFINE haemophilia A gene therapy study","author":"Pfizer\/Sangamo","year":"2022"},{"key":"10.1016\/j.blre.2022.101011_bb0530","series-title":"FDA places the Pfizer\/Sangamo Therapeutics phase 3 AFFINE haemophilia A gene therapy study on clinical hold","author":"FDA","year":"2021"},{"key":"10.1016\/j.blre.2022.101011_bb0535","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1365-2516.2010.02383.x","article-title":"Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels","volume":"17","author":"den Uijl","year":"2011","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0540","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1182\/bloodadvances.2018018226","article-title":"A cross-sectional analysis of cardiovascular disease in the hemophilia population","volume":"2","author":"Sood","year":"2018","journal-title":"Blood Adv"},{"key":"10.1016\/j.blre.2022.101011_bb0545","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/156652309787909490","article-title":"Hepatic gene transfer as a means of tolerance induction to transgene products","volume":"9","author":"LoDuca","year":"2009","journal-title":"Curr Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0550","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1182\/blood-2012-06-440123","article-title":"The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy","volume":"120","author":"Finn","year":"2012","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0555","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1182\/blood-2010-06-288001","article-title":"Eradication of neutralizing antibodies to factor VIII in canine hemophilia a after liver gene therapy","volume":"116","author":"Finn","year":"2010","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0560","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1182\/blood-2007-03-080093","article-title":"Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver","volume":"110","author":"Mingozzi","year":"2007","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0565","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/jth.13331","article-title":"Gene therapy for immune tolerance induction in hemophilia with inhibitors","volume":"14","author":"Arruda","year":"2016","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0570","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/hae.13717","article-title":"Members of working group tNSotSWofViGanbffr. The national blueprint for future factor VIII inhibitor clinical trials: NHLBI state of the science (SOS) workshop on factor VIII inhibitors","volume":"25","author":"Ragni","year":"2019","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0575","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1111\/hae.13762","article-title":"The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab","volume":"25","author":"Carcao","year":"2019","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0580","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1365-2141.2007.06657.x","article-title":"Inhibitor development in haemophilia B: an orphan disease in need of attention","volume":"138","author":"DiMichele","year":"2007","journal-title":"Br J Haematol"},{"key":"10.1016\/j.blre.2022.101011_bb0585","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1160\/TH17-01-0030","article-title":"Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX\/IXa and X\/Xa, emicizumab, depends on its ability to bridge the antigens","volume":"117","author":"Kitazawa","year":"2017","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0590","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model","volume":"18","author":"Kitazawa","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.blre.2022.101011_bb0595","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/ejh.13193","article-title":"Inhibitors in haemophilia A and B: management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients","volume":"102","author":"Ljung","year":"2019","journal-title":"Eur J Haematol"},{"key":"10.1016\/j.blre.2022.101011_bb0600","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1182\/blood-2003-03-0941","article-title":"Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS study group","volume":"102","author":"Gringeri","year":"2003","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0605","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.2174\/138161211797247541","article-title":"Perinatal gene transfer to the liver","volume":"17","author":"McKay","year":"2011","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.blre.2022.101011_bb0610","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/hgtb.2012.243","article-title":"Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy","volume":"24","author":"Louis Jeune","year":"2013","journal-title":"Human Gene Ther Methods"},{"key":"10.1016\/j.blre.2022.101011_bb0615","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/hae.14431","article-title":"Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors","volume":"28","author":"Di Minno","year":"2022","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0620","first-page":"55","article-title":"Body length and organ weights of infants and children: a study of the body length and normal weights of the more important vital organs of the body between birth and twelve years of age","volume":"9","author":"Coppoletta","year":"1933","journal-title":"Am J Pathol"},{"key":"10.1016\/j.blre.2022.101011_bb0625","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.transci.2019.08.012","article-title":"Gene therapy for hemophilia: progress to date and challenges moving forward","volume":"58","author":"Gollomp","year":"2019","journal-title":"Transfus Apher Sci"},{"key":"10.1016\/j.blre.2022.101011_bb0630","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aav7325","article-title":"Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates","volume":"11","author":"Milani","year":"2019","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.blre.2022.101011_bb0635","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1182\/hematology.2021000254","article-title":"Hemophilia gene therapy: ushering in a new treatment paradigm?","volume":"2021","author":"George","year":"2021","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"10.1016\/j.blre.2022.101011_bb0640","article-title":"CRISPR\/Cas9-mediated targeted insertion of human F9 achieves therapeutic circulating protein levels in mice and non-human primates","author":"Huang","year":"2019","journal-title":"Am Soc Gene Cell Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0645","doi-asserted-by":"crossref","first-page":"277ra28","DOI":"10.1126\/scitranslmed.aaa1405","article-title":"Liver-directed lentiviral gene therapy in a dog model of hemophilia B","volume":"7","author":"Cantore","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.blre.2022.101011_bb0650","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1038\/ncomms3773","article-title":"Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A","volume":"4","author":"Du","year":"2013","journal-title":"Nat Commun"},{"key":"10.1016\/j.blre.2022.101011_bb0655","doi-asserted-by":"crossref","first-page":"6114","DOI":"10.1182\/blood-2010-06-293308","article-title":"In vivo efficacy of platelet-delivered, high specific activity factor VIII variants","volume":"116","author":"Greene","year":"2010","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0660","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1172\/JCI28416","article-title":"Factor VIII ectopically targeted to platelets is therapeutic in hemophilia a with high-titer inhibitory antibodies","volume":"116","author":"Shi","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1016\/j.blre.2022.101011_bb0665","first-page":"935","article-title":"Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice","volume":"118","author":"Follenzi","year":"2008","journal-title":"J Clin Invest"},{"key":"10.1016\/j.blre.2022.101011_bb0670","article-title":"Progress in the development of anti-tissue factor pathway inhibitors for Haemophilia management","volume":"8","author":"Mahlangu","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.blre.2022.101011_bb0675","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1111\/jth.15270","article-title":"Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-results of the phase 1 inhibitor cohort","volume":"19","author":"Pasi","year":"2021","journal-title":"J Thromb Haemostasis"},{"key":"10.1016\/j.blre.2022.101011_bb0680","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1182\/bloodadvances.2021006119","article-title":"Efanesoctocog alfa for hemophilia A: results from a phase 1 repeat-dose study","volume":"6","author":"Lissitchkov","year":"2022","journal-title":"Blood Adv"},{"key":"10.1016\/j.blre.2022.101011_bb0685","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1056\/NEJMe2024545","article-title":"Treatment of hemophilia - more amazing progress","volume":"383","author":"Mannucci","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0690","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa2002699","article-title":"BIVV001 fusion protein as factor VIII replacement therapy for hemophilia A","volume":"383","author":"Konkle","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.blre.2022.101011_bb0695","first-page":"479","article-title":"Factor VIII replacement is still the standard of care in haemophilia A","volume":"17","author":"Aledort","year":"2019","journal-title":"Blood Transfus"},{"key":"10.1016\/j.blre.2022.101011_bb0700","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1055\/s-0040-1718887","article-title":"Enhanced half-life recombinant factor VIII concentrates for hemophilia A: insights from pivotal and extension studies","volume":"47","author":"Di Minno","year":"2021","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.blre.2022.101011_bb0705","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000144","article-title":"Navigating speed bumps on the innovation highway in hemophilia therapeutics","volume":"2","author":"DiMichele","year":"2018","journal-title":"HemaSphere."},{"key":"10.1016\/j.blre.2022.101011_bb0710","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1111\/hae.12294","article-title":"Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three-times-weekly prophylaxis with rFVIII-FS","volume":"20","author":"Lalezari","year":"2014","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0715","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/jth.14469","article-title":"Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: is there a difference?","volume":"17","author":"Carcao","year":"2019","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0720","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1182\/blood-2011-09-382846","article-title":"Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia a patients","volume":"119","author":"Powell","year":"2012","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0725","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1111\/jth.14153","article-title":"Pharmacokinetics and the transition to extended half-life factor concentrates: communication from the SSC of the ISTH","volume":"16","author":"Ragni","year":"2018","journal-title":"J Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0730","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1055\/s-0040-1709519","article-title":"Modeling to predict factor VIII levels associated with zero bleeds in patients with severe hemophilia a initiated on tertiary prophylaxis","volume":"120","author":"Chowdary","year":"2020","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0735","first-page":"3668","article-title":"Use of bypassing agents prior to and post bypassing agent dosing guidance during emicizumab prophylaxis: analyses from the HAVEN 1 study","author":"Callaghan","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.blre.2022.101011_bb0740","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/hae.14078","article-title":"i Psg. Biological mechanisms underlying inter-individual variation in factor VIII clearance in haemophilia","volume":"26","author":"Turecek","year":"2020","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0745","article-title":"Paradigm shift for the treatment of hereditary haemophilia: towards precision medicine","volume":"100618","author":"Spadarella","year":"2019","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0750","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1128\/CVI.05107-11","article-title":"Adeno-associated virus antibody profiles in newborns, children, and adolescents","volume":"18","author":"Calcedo","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"10.1016\/j.blre.2022.101011_bb0755","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3389\/fimmu.2013.00341","article-title":"Humoral immune response to AAV","volume":"4","author":"Calcedo","year":"2013","journal-title":"Front Immunol"},{"key":"10.1016\/j.blre.2022.101011_bb0760","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/gt.2011.90","article-title":"Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia","volume":"19","author":"Li","year":"2012","journal-title":"Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0765","series-title":"Follow-up of more than 5 years in a cohort of patients with hemophilia B treated with fidanacogene elaparvovec adeno-associated virus gene therapy","author":"Samelson-Jones","year":"2021"},{"key":"10.1016\/j.blre.2022.101011_bb0770","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1055\/s-0041-1722862","article-title":"Gene therapy for inherited bleeding disorders","volume":"47","author":"Arruda","year":"2021","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.blre.2022.101011_bb0775","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1182\/blood-2002-09-2889","article-title":"Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway","volume":"102","author":"Davidoff","year":"2003","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0780","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ymthe.2005.09.003","article-title":"High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses","volume":"13","author":"De","year":"2006","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0785","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1089\/hum.2009.031","article-title":"Effect of adeno-associated virus serotype and genomic structure on liver transduction and biodistribution in mice of both genders","volume":"20","author":"Paneda","year":"2009","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0790","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1182\/blood-2004-10-3867","article-title":"Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2\/8-mediated, liver-directed gene therapy","volume":"105","author":"Wang","year":"2005","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0795","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/j.ymthe.2017.04.003","article-title":"In utero transfer of adeno-associated viral vectors produces long-term factor IX levels in a cynomolgus macaque model","volume":"25","author":"Mattar","year":"2017","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0800","first-page":"499","article-title":"Investigational hemophilia a gene therapy shows sustained benefit","volume":"323","author":"Abbasi","year":"2020","journal-title":"JAMA."},{"key":"10.1016\/j.blre.2022.101011_bb0805","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/rth2.12195","article-title":"Hemophilia trials in the twenty-first century: defining patient important outcomes","volume":"3","author":"Konkle","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"key":"10.1016\/j.blre.2022.101011_bb0810","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/j.1365-2516.2011.02539.x","article-title":"Clinical severity of haemophilia a: does the classification of the 1950s still stand?","volume":"17","author":"Den Uijl","year":"2011","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0815","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1182\/bloodadvances.2018020552","article-title":"The frequency of joint hemorrhages and procedures in nonsevere hemophilia A vs B","volume":"2","author":"Soucie","year":"2018","journal-title":"Blood Adv"},{"key":"10.1016\/j.blre.2022.101011_bb0820","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/hae.13353","article-title":"Improved joint health in subjects with severe haemophilia a treated prophylactically with recombinant factor VIII Fc fusion protein","volume":"24","author":"Oldenburg","year":"2018","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0825","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1055\/s-0036-1579640","article-title":"Assessment of hemophilic Arthropathy by ultrasound: where do we stand?","volume":"42","author":"Di Minno","year":"2016","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.blre.2022.101011_bb0830","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/bjh.17919","article-title":"Diagnosis and treatment of chronic synovitis in patients with haemophilia: consensus statements from the Italian Association of Haemophilia Centres","volume":"196","author":"Di Minno","year":"2022","journal-title":"Br J Haematol"},{"issue":"Suppl. 3","key":"10.1016\/j.blre.2022.101011_bb0835","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/hae.14099","article-title":"Outcome measures in Haemophilia: beyond ABR (annualized bleeding rate)","volume":"27","author":"Manco-Johnson","year":"2021","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0840","doi-asserted-by":"crossref","DOI":"10.1111\/hae.13504","article-title":"Core outcome set for gene therapy in haemophilia: results of the coreHEM multistakeholder project","volume":"24","author":"Iorio","year":"2018","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0845","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.ymthe.2006.03.002","article-title":"Inadvertent germline transmission of AAV2 vector: findings in a rabbit model correlate with those in a human clinical trial","volume":"13","author":"Schuettrumpf","year":"2006","journal-title":"Mol Ther"},{"key":"10.1016\/j.blre.2022.101011_bb0850","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/hae.14015","article-title":"World federation of hemophilia gene therapy registry","volume":"26","author":"Konkle","year":"2020","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0855","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.jval.2018.12.004","article-title":"Are payers ready, willing, and able to provide access to new durable gene therapies?","volume":"22","author":"Barlow","year":"2019","journal-title":"Value Health"},{"key":"10.1016\/j.blre.2022.101011_bb0860","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1182\/bloodadvances.2018021345","article-title":"Gene therapy in hemophilia A: a cost-effectiveness analysis","volume":"2","author":"Machin","year":"2018","journal-title":"Blood Adv"},{"key":"10.1016\/j.blre.2022.101011_bb0865","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13023-020-01555-w","article-title":"Optimizing language for effective communication of gene therapy concepts with hemophilia patients: a qualitative study","volume":"16","author":"Hart","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.blre.2022.101011_bb0870","doi-asserted-by":"crossref","DOI":"10.1111\/hae.14313","article-title":"Comparative analysis of the pivotal studies of extended half-life recombinant FVIII products for treatment of haemophilia A","volume":"27","author":"Mannucci","year":"2021","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0875","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2020009217","article-title":"Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies","volume":"137","author":"Callaghan","year":"2021","journal-title":"Blood."},{"key":"10.1016\/j.blre.2022.101011_bb0880","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/17474086.2018.1423961","article-title":"Measuring success in hemophilia gene therapy using a factor level & outcomes yardstick","volume":"11","author":"Machin","year":"2018","journal-title":"Expert Rev Hematol"},{"key":"10.1016\/j.blre.2022.101011_bb0885","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/hae.13769","article-title":"How to discuss gene therapy for haemophilia? A patient and physician perspective","volume":"25","author":"Miesbach","year":"2019","journal-title":"Haemophilia"},{"key":"10.1016\/j.blre.2022.101011_bb0890","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2019.100618","article-title":"Paradigm shift for the treatment of hereditary haemophilia: towards precision medicine","volume":"39","author":"Spadarella","year":"2020","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0895","doi-asserted-by":"crossref","first-page":"767","DOI":"10.2147\/PPA.S239810","article-title":"The patient experience of gene therapy for hemophilia: qualitative interviews with trial patients","volume":"14","author":"Miesbach","year":"2020","journal-title":"Patient Prefer Adherence"},{"key":"10.1016\/j.blre.2022.101011_bb0900","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2021.100828","article-title":"Post-authorization pharmacovigilance for hemophilia in Europe and the USA: Independence and transparency are keys","volume":"49","author":"Peyvandi","year":"2021","journal-title":"Blood Rev"},{"key":"10.1016\/j.blre.2022.101011_bb0905","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-pharmtox-010818-021625","article-title":"Surviving in the valley of death: opportunities and challenges in translating academic drug discoveries","volume":"59","author":"Parrish","year":"2019","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.blre.2022.101011_bb0910","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1093\/eurheartj\/ehv226","article-title":"Cardiovascular precision medicine: hope or hype?","volume":"36","author":"Pitt","year":"2015","journal-title":"Eur Heart J"},{"key":"10.1016\/j.blre.2022.101011_bb0915","series-title":"BioMarin reports a serious adverse event for its phase I\/II gene therapy trial for haemophilia A","author":"Inc. BP","year":"2022"}],"container-title":["Blood Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0268960X22000856?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0268960X22000856?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T20:30:24Z","timestamp":1759437024000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0268960X22000856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":183,"alternative-id":["S0268960X22000856"],"URL":"https:\/\/doi.org\/10.1016\/j.blre.2022.101011","relation":{},"ISSN":["0268-960X"],"issn-type":[{"value":"0268-960X","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Progress, and prospects in the therapeutic armamentarium of persons with congenital hemophilia. Defining the place for liver-directed gene therapy","name":"articletitle","label":"Article Title"},{"value":"Blood Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.blre.2022.101011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"101011"}}