References
  1. World Federation of Haemophilia (2019) Report on the Annual Global Survey 2018. WFH, Montreal, Canada.http://www1.wfh.org/publications/files/pdf-1731.pdf. Accessed May 20, 2020
  2. Regulation (EC) No. 141/2000 of the European Parliament and of the Council.https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141&from=EN. Accessed May 20, 2020.
  3. Giannelli F, Green PM. The molecular basis of haemophilia A and B. Baillieres Clin Haematol . 1996;9(2):211-228. doi:10.1016/s0950-3536(96)80059-x.
  4. Weyand AC, Pipe SW. New therapies for hemophilia. Blood . 2019;133(5):389-398. doi:10.1182/blood-2018-08-872291.
  5. Perrin GQ, Herzog RW, Markusic DM. Update on clinical gene therapy for hemophilia. Blood . 2019;133(5):407-414. doi:10.1182/blood-2018-07-820720.
  6. Pasi KJ, Rangarajan S, Mitchell N, et al. Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med . 2020;382(1):29-40. doi:10.1056/NEJMoa1908490.
  7. Iorio A, Stonebraker JS, Chambost H, et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med . 2019;171(8):540-546. doi:10.7326/M19-1208.
  8. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia . 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x.
  9. White GC 2nd, Kempton CL, Grimsley A, Nielsen B, Roberts HR. Cellular immune responses in hemophilia: why do inhibitors develop in some, but not all hemophiliacs?. J Thromb Haemost . 2005;3(8):1676-1681. doi:10.1111/j.1538-7836.2005.01375.x,
  10. Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood . 2015;125(13):2038-2044. doi:10.1182/blood-2015-01-528414.
  11. Mazepa MA, Monahan PE, Baker JR, Riske BK, Soucie JM; US Hemophilia Treatment Center Network. Men with severe hemophilia in the United States: birth cohort analysis of a large national database. Blood . 2016;127(24):3073-3081. doi:10.1182/blood-2015-10-675140.
  12. Di Minno MND, Pasta G, Airaldi S, et al. Ultrasound for Early Detection of Joint Disease in Patients with Hemophilic Arthropathy. J Clin Med . 2017;6(8):77. doi:10.3390/jcm6080077.
  13. Shima M, Hanabusa H, Taki M, et al. Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med . 2016;374(21):2044-2053. doi:10.1056/NEJMoa1511769.
  14. Roche’s Hemlibra reduced treated bleeds by 96 percent compared to no prophylaxis in phase III HAVEN 3 study in haemophilia A without factor VIII inhibitors.https://www.roche.com/media/releases/med-cor-2018-05-21.htm. Accessed on May 20, 2020.
  15. Miyazaki, K. (2013) Coagulation of Blood. In: Gellman M.D., Turner J.R. (eds) Encyclopedia of Behavioral Medicine. Springer, New York, NY.
  16. Shetty S, Vora S, Kulkarni B, et al. Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients. Br J Haematol . 2007;138(4):541-544. doi:10.1111/j.1365-2141.2007.06693.x.
  17. Pasi KJ, Rangarajan S, Georgiev P, et al. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med . 2017;377(9):819-828. doi:10.1056/NEJMoa1616569.
  18. Machin N, Ragni MV. An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. J Blood Med . 2018;9:135-140. doi:10.2147/JBM.S159297.
  19. Farkas AM, Mariz S, Stoyanova-Beninska V, et al. Advanced Therapy Medicinal Products for Rare Diseases: State of Play of Incentives Supporting Development in Europe. Front Med (Lausanne) . 2017;4:53. Published 2017 May 16. doi:10.3389/fmed.2017.00053.
  20. Chuah MK, Evens H, VandenDriessche T. Gene therapy for hemophilia. J Thromb Haemost . 2013;11 Suppl 1:99-110. doi:10.1111/jth.12215.
  21. Swystun LL, Lillicrap D. Gene Therapy for Coagulation Disorders. Circ Res . 2016;118(9):1443-1452. doi:10.1161/CIRCRESAHA.115.307015.
  22. Chapin JC, Monahan PE. Gene Therapy for Hemophilia: Progress to Date. BioDrugs . 2018;32(1):9-25. doi:10.1007/s40259-017-0255-0.
  23. Atchison RW, Casto BC, Hammon WM. Adenovirus-associated defective virus particles. Science . 1965;149(3685):754-756. doi:10.1126/science.149.3685.754.
  24. ClinicalTrials.gov.https://clinicaltrials.gov/ct2/home. Accessed on May 20, 2020.
  25. EU Clinical Trials Register.https://www.clinicaltrialsregister.eu/. Accessed on May20, 2020.
  26. Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med . 2014;371(21):1994-2004. doi:10.1056/NEJMoa1407309.
  27. Doshi BS, Arruda VR. Gene therapy for hemophilia: what does the future hold?. Ther Adv Hematol . 2018;9(9):273-293. Published 2018 Aug 27. doi:10.1177/2040620718791933.
  28. Ide LM, Gangadharan B, Chiang KY, Doering CB, Spencer HT. Hematopoietic stem-cell gene therapy of hemophilia A incorporating a porcine factor VIII transgene and nonmyeloablative conditioning regimens. Blood . 2007;110(8):2855-2863. doi:10.1182/blood-2007-04-082602.
  29. Sangamo Therapeutics (2018). Sangamo announces treatment of first patient in phase 1/2 clinical trial of in vivo genome editing therapy for hemophilia B.https://investor.sangamo.com/news-releases/news-release-details/sangamo-announces-treatment-first-patient-phase-12-clinical-0. Accessed on May 20, 2020.
  30. Herzog RW. Hemophilia Gene Therapy: Caught Between a Cure and an Immune Response. Mol Ther . 2015;23(9):1411-1412. doi:10.1038/mt.2015.135.
  31. Mingozzi F, High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood . 2013;122(1):23-36. doi:10.1182/blood-2013-01-306647.