Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
World Academy of Sciences Journal
Join Editorial Board Propose a Special Issue
Print ISSN: 2632-2900 Online ISSN: 2632-2919
Journal Cover
May-June 2025 Volume 7 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-June 2025 Volume 7 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Gene therapy for hemophilia: Recent developments and challenges (Review)

  • Authors:
    • Marwa Ali Abdulnabi
    • Enass Abdul Kareem Dagher Al‑Saadi
    • Israa M. Al‑Bayaa
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Al-Kindy College of Medicine, University of Baghdad, Baghdad 10045, Iraq, Department of Pathology, College of Medicine, University of Kerbala, Kerbala 56001, Iraq
    Copyright: © Ali Abdulnabi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 41
    |
    Published online on: February 28, 2025
       https://doi.org/10.3892/wasj.2025.329
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

 Hemophilia is an X‑linked disease marked by the absence or impaired function of specific coagulation factors. Hemophilia A is characterized by a deficiency in factor VIII, and hemophilia B is characterized by a deficiency in factor IX. Factor XI deficiency, referred to as hemophilia C, is a very uncommon bleeding illness characterized by moderate symptoms; although the condition is not widespread, standard management poses significant challenges linked to socioeconomic factors. The introduction of FDA‑approved gene therapy for hemophilia B in 2022 holds transformative potential; however, certain issues demand careful consideration. The present review provides insight into the existing hemophilia landscape, discusses the latest strides in gene therapy for hemophilia, and examines the hurdles that need to be addressed to make this innovative treatment more accessible to individuals afflicted by this condition.
View Figures

Figure 1

View References

1 

Bolton-Maggs PH and Pasi KJ: Haemophilias A and B. Lancet. 361:1801–1809. 2003.PubMed/NCBI View Article : Google Scholar

2 

Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C and Germini F: Data and Demographics Committee of the World Federation of Hemophilia. Establishing the prevalence and prevalence at birth of hemophilia in males: A meta-analytic approach using national registries. Ann Intern Med. 171:540–546. 2019.PubMed/NCBI View Article : Google Scholar

3 

Kavaklı K, Antmen B, Okan V, Şahin F, Aytaç S, Balkan C, Berber E, Kaya Z, Küpesiz A and Zülfikar B: Gene therapy in haemophilia: Literature review and regional perspectives for Turkey. Ther Adv Hematol. 13(20406207221104591)2022.PubMed/NCBI View Article : Google Scholar

4 

Bolous NS, Bhatt N, Bhakta N, Neufeld EJ, Davidoff AM and Reiss UM: Gene therapy and hemophilia: Where do we go from here? J Blood Med. 13:559–580. 2022.PubMed/NCBI View Article : Google Scholar

5 

World Federation of Hemophilia: The report on the WFH annual global survey 2020: World Federation of Hemophilia, 2021. Available from: https://www1.wfh.org/publications/files/pdf-2045.pdf.

6 

Kadhim KAR, Al-Lami FH and Baldawi KH: Epidemiological profile of hemophilia in Baghdad-Iraq. Inquiry. 56(46958019845280)2019.PubMed/NCBI View Article : Google Scholar

7 

Abdulsalam AH, Al-Rahal NK and Ghiath Y: Inherited bleeding disorders in pediatric patients; experience of the national referral center in Iraq. Indian J Hematol Blood Transfus. 37:96–100. 2021.PubMed/NCBI View Article : Google Scholar

8 

Hassan S, Monahan RC, Mauser-Bunschoten EP, van Vulpen LFD, Eikenboom J, Beckers EAM, Hooimeijer L, Ypma PF, Nieuwenhuizen L, Coppens M, et al: Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018. J Thromb Haemost. 19:645–653. 2021.PubMed/NCBI View Article : Google Scholar

9 

Coffin D, Gouider E, Konkle B, Hermans C, Lambert C, Diop S, Ayoub E, Tootoonchian E, Youttananukorn T, Dakik P, et al: The world federation of hemophilia world bleeding disorders registry: Insights from the first 10,000 patients. Res Pract Thromb Haemost. 7(102264)2023.PubMed/NCBI View Article : Google Scholar

10 

Taresh AK and Hassan MK: Inhibitors among patients with hemophilia in Basra, Iraq-A single center experience. Niger J Clin Pract. 22:416–421. 2019.PubMed/NCBI View Article : Google Scholar

11 

Lateef IA: Evaluation of the clinical status of patients with inherited bleeding disorders in Diyala-Iraq. Diyala J Medicine. 9:23–29. 2015.

12 

Lateef IA, Hamood HJ and Khaleel OA: Spectrum of hemophilia in Diyala-Iraq. Diyala J Medicine. 10:53–58. 2016.

13 

Sharma A, Mathew ME, Sriganesh V and Reiss UM: Gene therapy for haemophilia. Cochrane Database Syst Rev. 4(CD010822)2020.PubMed/NCBI View Article : Google Scholar

14 

Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, et al: WFH guidelines for the management of hemophilia. Haemophilia. 26:1–158. 2020.PubMed/NCBI View Article : Google Scholar

15 

Nathwani AC: Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019:1–8. 2019.PubMed/NCBI View Article : Google Scholar

16 

Wang X, Shin SC, Chiang AF, Khan I, Pan D, Rawlings DJ and Miao CH: Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A. Mol Ther. 23:617–626. 2015.PubMed/NCBI View Article : Google Scholar

17 

Doncel SS, Mosquera GA, Pelaez RG, Cortes JM, Rico CA, Cadavid FJ, Plazas NR, Amar IAP, Siado JEP, Rey FAP, et al: Genetic characterization of the factor VIII gene in a cohort of colombian patients with severe hemophilia A with inhibitors. Hematol Rep. 14:149–154. 2022.PubMed/NCBI View Article : Google Scholar

18 

Hassan MM and Jabber AD: Identification of factor VIII gene mutations in Iraqi patient with hemophilia A. Int J Med Res Prof. 2:192–199. 2016.

19 

Abdulqader AMR, Mohammed AI, Rachid S, Ghoraishizadeh P and Mahmood SN: Identification of the intron 22 and intron 1 inversions of the factor VIII gene in Iraqi Kurdish patients with hemophilia A. Clin Appl Thromb Hemost. 26(1076029619888293)2020.PubMed/NCBI View Article : Google Scholar

20 

Lisowski L, Staber JM, Wright JF and Valentino LA: The intersection of vector biology, gene therapy, and hemophilia. Res Pract Thromb Haemost. 5(e12586)2021.PubMed/NCBI View Article : Google Scholar

21 

Palmer TD, Thompson AR and Miller AD: Production of human factor IX in animals by genetically modified skin fibroblasts: Potential therapy for hemophilia B. Blood. 73:438–445. 1989.PubMed/NCBI

22 

Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, et al: Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 365:2357–2365. 2011.PubMed/NCBI View Article : Google Scholar

23 

Niemeyer GP, Herzog RW, Mount J, Arruda VR, Tillson DM, Hathcock J, van Ginkel FW, High KA and Lothrop CD Jr: Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood. 113:797–806. 2009.PubMed/NCBI View Article : Google Scholar

24 

Liao G, Nayak S, Regueiro JR, Berger SB, Detre C, Romero X, de Waal Malefyt R, Chatila TA, Herzog RW and Terhorst C: GITR engagement preferentially enhances proliferation of functionally competent CD4+ CD25+ FoxP3+ regulatory T cells. Int Immunol. 22:259–270. 2010.PubMed/NCBI View Article : Google Scholar

25 

Cooper M, Nayak S, Hoffman BE, Terhorst C, Cao O and Herzog RW: Improved induction of immune tolerance to factor IX by hepatic AAV-8 gene transfer. Hum Gene Ther. 20:767–776. 2009.PubMed/NCBI View Article : Google Scholar

26 

Mátrai J, Chuah MKL and VandenDriessche T: Preclinical and clinical progress in hemophilia gene therapy. Curr Opin Hematol. 17:387–392. 2010.PubMed/NCBI View Article : Google Scholar

27 

Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY and Pasi KJ: AAV5-factor VIII gene transfer in severe hemophilia A. N Engl J Med. 377:2519–2530. 2017.PubMed/NCBI View Article : Google Scholar

28 

Guo XL, Chung TH, Qin Y, Zheng J, Zheng H, Sheng L, Wynn T and Chang LJ: Hemophilia gene therapy: New development from bench to bed side. Curr Gene Ther. 19:264–273. 2019.PubMed/NCBI View Article : Google Scholar

29 

Xu L, Nichols TC, Sarkar R, McCorquodale S, Bellinger DA and Ponder KP: Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy. Proc Natl Acad Sci USA. 102:6080–6085. 2005.PubMed/NCBI View Article : Google Scholar

30 

Milani M, Canepari C, Liu T, Biffi M, Russo F, Plati T, Curto R, Patarroyo-White S, Drager D, Visigalli I, et al: Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates. Nat Commun. 13(2454)2022.PubMed/NCBI View Article : Google Scholar

31 

Tsui LV, Kelly M, Zayek N, Rojas V, Ho K, Ge Y, Moskalenko M, Mondesire J, Davis J, Roey MV, et al: Production of human clotting Factor IX without toxicity in mice after vascular delivery of a lentiviral vector. Nat Biotechnol. 20:53–57. 2002.PubMed/NCBI View Article : Google Scholar

32 

Stein CS, Kang Y, Sauter SL, Townsend K, Staber P, Derksen TA, Martins I, Qian J, Davidson BL and McCray PB Jr: In vivo treatment of hemophilia A and mucopolysaccharidosis type VII using nonprimate lentiviral vectors. Mol Ther. 3:850–856. 2001.PubMed/NCBI View Article : Google Scholar

33 

Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D and Naldini L: A third-generation lentivirus vector with a conditional packaging system. J Virol. 72:8463–8471. 1998.PubMed/NCBI View Article : Google Scholar

34 

Kuether EL, Schroeder JA, Fahs SA, Cooley BC, Chen Y, Montgomery RR, Wilcox DA and Shi Q: Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity. J Thromb Haemost. 10:1570–1580. 2012.PubMed/NCBI View Article : Google Scholar

35 

Roth DA, Tawa NE Jr, O'Brien JM, Treco DA and Selden RF: Factor VIII Transkaryotic Therapy Study Group. Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A. N Engl J Med. 344:1735–1742. 2001.PubMed/NCBI View Article : Google Scholar

36 

Spira J, Plyushch OP, Andreeva TA and Andreev Y: Prolonged bleeding-free period following prophylactic infusion of recombinant factor VIII reconstituted with pegylated liposomes. Blood. 108:3668–3673. 2006.PubMed/NCBI View Article : Google Scholar

37 

Di Minno G, Cerbone AM, Coppola A, Cimino E, Di Capua M, Pamparana F, Tufano A and Di Minno MN: Longer-acting factor VIII to overcome limitations in haemophilia management: The PEGylated liposomes formulation issue. Haemophilia. 16:2–6. 2010.PubMed/NCBI View Article : Google Scholar

38 

Lu DR, Zhou JM, Zheng B, Qiu XF, Xue JL, Wang JM, Meng PL, Han FL, Ming BH and Wang XP: Stage I clinical trial of gene therapy for hemophilia B. Sci China B. 36:1342–1351. 1993.PubMed/NCBI

39 

Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, et al: Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med. 12:342–347. 2006.PubMed/NCBI View Article : Google Scholar

40 

Crudele JM, Finn JD, Siner JI, Martin NB, Niemeyer GP, Zhou S, Mingozzi F, Lothrop CD Jr and Arruda VR: AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood. 125:1553–1561. 2015.PubMed/NCBI View Article : Google Scholar

41 

Von Drygalski A, Giermasz A, Castaman G, Key NS, Lattimore S, Leebeek FWG, Miesbach W, Recht M, Long A, Gut R, et al: Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 3:3241–3247. 2019.PubMed/NCBI View Article : Google Scholar

42 

Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, Lattimore S, Peerlinck K, Van der Valk P, Coppens M, et al: Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 388:706–718. 2023.PubMed/NCBI View Article : Google Scholar

43 

Pipe SW, Reddy KR and Chowdary P: Gene therapy: Practical aspects of implementation. Haemophilia. 28 (Suppl 4):S44–S52. 2022.PubMed/NCBI View Article : Google Scholar

44 

Pasi KJ, Laffan M, Rangarajan S, Robinson TM, Mitchell N, Lester W, Symington E, Madan B, Yang X, Kim B, et al: Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 27:947–956. 2021.PubMed/NCBI View Article : Google Scholar

45 

Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF and Wong WY: Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med. 382:29–40. 2020.PubMed/NCBI View Article : Google Scholar

46 

Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, et al: Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 386:1013–1025. 2022.PubMed/NCBI View Article : Google Scholar

47 

Long BR, Veron P, Kuranda K, Hardet R, Mitchell N, Hayes GM, Wong WY, Lau K, Li M, Hock MB, et al: Early phase clinical immunogenicity of valoctocogene roxaparvovec, an AAV5-mediated gene therapy for hemophilia A. Mol Ther. 29:597–610. 2021.PubMed/NCBI View Article : Google Scholar

48 

Visweshwar N, Harrington TJ, Leavitt AD, Konkle BA, Giermasz A, Stine K, et al: Updated results of the alta study, a phase 1/2 study of giroctocogene fitelparvovec (PF-07055480/SB-525) gene therapy in adults with severe hemophilia A. Blood. 138 (Suppl 1)(564)2021.

49 

Elkouby L, Armour SM, Toso R, DiPietro M, Davidson RJ, Nguyen GN, Willet M, Kutza S, Silverberg J, Frick J, et al: Preclinical assessment of an optimized AAV-FVIII vector in mice and non-human primates for the treatment of hemophilia A. Mol Ther Methods Clin Dev. 24:20–29. 2022.PubMed/NCBI View Article : Google Scholar

50 

George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, et al: Multiyear factor VIII expression after AAV gene transfer for hemophilia A. N Engl J Med. 385:1961–1973. 2021.PubMed/NCBI View Article : Google Scholar

51 

Barbon E, Ayme G, Mohamadi A, Ottavi JF, Kawecki C, Casari C, Verhenne S, Marmier S, van Wittenberghe L, Charles S, et al: Single-domain antibodies targeting antithrombin reduce bleeding in hemophilic mice with or without inhibitors. EMBO Mol Med. 12(e11298)2020.PubMed/NCBI View Article : Google Scholar

52 

Setten RL, Rossi JJ and Han SP: The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 18:421–446. 2019.PubMed/NCBI View Article : Google Scholar

53 

Patnaik MM and Moll S: Inherited antithrombin deficiency: A review. Haemophilia. 14:1229–1239. 2008.PubMed/NCBI View Article : Google Scholar

54 

Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, et al: Targeting of antithrombin in hemophilia A or B with RNAi therapy. N Engl J Med. 377:819–828. 2017.PubMed/NCBI View Article : Google Scholar

55 

Dargaud Y, Béguin S, Lienhart A, Al Dieri R, Trzeciak C, Bordet JC, Hemker HC and Negrier C: Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost. 93:475–480. 2005.PubMed/NCBI View Article : Google Scholar

56 

Segurado OG, Jiang R and Pipe SW: Challenges and opportunities when transitioning from in vivo gene replacement to in vivo CRISPR/Cas9 therapies-a spotlight on hemophilia. Expert Opin Biol Ther. 22:1091–1098. 2022.PubMed/NCBI View Article : Google Scholar

57 

Chen H, Shi M, Gilam A, Zheng Q, Zhang Y, Afrikanova I, Li J, Gluzman Z, Jiang R, Kong LJ, et al: Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human factor VIII. Sci Rep. 9(16838)2019.PubMed/NCBI View Article : Google Scholar

58 

Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, Rohde ME, Wong SY, Davidson RJ, Zhou S, et al: Robust ZFN-mediated genome editing in adult hemophilic mice. Blood. 122:3283–3287. 2013.PubMed/NCBI View Article : Google Scholar

59 

Shi Q: Platelet-targeted gene therapy for hemophilia. Mol Ther Methods Clin Dev. 9:100–108. 2018.PubMed/NCBI View Article : Google Scholar

60 

Nayak S and Herzog RW: Progress and prospects: Immune responses to viral vectors. Gene Ther. 17:295–304. 2010.PubMed/NCBI View Article : Google Scholar

61 

Salas D, Kwikkers KL, Zabaleta N, Bazo A, Petry H, van Deventer SJ, Aseguinolaza GG and Ferreira V: Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates. Blood Adv. 3:2632–2641. 2019.PubMed/NCBI View Article : Google Scholar

62 

Ferla R, Claudiani P, Savarese M, Kozarsky K, Parini R, Scarpa M, Donati MA, Sorge G, Hopwood JJ, Parenti G, et al: Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial. Hum Gene Ther. 26:145–152. 2015.PubMed/NCBI View Article : Google Scholar

63 

Elmore ZC, Oh DK, Simon KE, Fanous MM and Asokan A: Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme. JCI Insight. 5(e139881)2020.PubMed/NCBI View Article : Google Scholar

64 

Follenzi A, Santambrogio L and Annoni A: Immune responses to lentiviral vectors. Curr Gene Ther. 7:306–315. 2007.PubMed/NCBI View Article : Google Scholar

65 

Limberis MP, Bell CL, Heath J and Wilson JM: Activation of transgene-specific T cells following lentivirus-mediated gene delivery to mouse lung. Mol Ther. 18:143–150. 2010.PubMed/NCBI View Article : Google Scholar

66 

Geisler A and Fechner H: MicroRNA-regulated viral vectors for gene therapy. World J Exp Med. 6:37–54. 2016.PubMed/NCBI View Article : Google Scholar

67 

Chen Y, Schroeder JA, Gao C, Li J, Hu J and Shi Q: In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy. J Cell Physiol. 236:354–365. 2021.PubMed/NCBI View Article : Google Scholar

68 

Lundstrom K: Viral vectors in gene therapy: Where do we stand in 2023? Viruses. 15(698)2023.PubMed/NCBI View Article : Google Scholar

69 

Nathwani AC, Rosales C, McIntosh J, Rastegarlari G, Nathwani D, Raj D, Nawathe S, Waddington SN, Bronson R, Jackson S, et al: Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther. 19:876–885. 2011.PubMed/NCBI View Article : Google Scholar

70 

Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Peruta MD, Lheriteau E, Patel N, Raj D, et al: Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 371:1994–2004. 2014.PubMed/NCBI View Article : Google Scholar

71 

Batty P and Lillicrap D: Hemophilia gene therapy: Approaching the first licensed product. Hemasphere. 5(e540)2021.PubMed/NCBI View Article : Google Scholar

72 

Chandler RJ, LaFave MC, Varshney GK, Trivedi NS, Carrillo-Carrasco N, Senac JS, Wu W, Hoffmann V, Elkahloun AG, Burgess SM and Venditti CP: Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Invest. 125:870–880. 2015.PubMed/NCBI View Article : Google Scholar

73 

Fong S, Rangarajan S and Mitchell N: First in human liver biopsy study following gene therapy for hemophilia A. Res Pract Thromb Haemost. 4(3)2020.

74 

Marcucci KT, Jadlowsky JK, Hwang WT, Suhoski-Davis M, Gonzalez VE, Kulikovskaya I, Gupta M, Lacey SF, Plesa G, Chew A, et al: Retroviral and lentiviral safety analysis of gene-modified T cell products and infused HIV and oncology patients. Mol Ther. 26:269–279. 2018.PubMed/NCBI View Article : Google Scholar

75 

Arruda VR, Fields PA, Milner R, Wainwright L, De Miguel MP, Donovan PJ, Herzog RW, Nichols TC, Biegel JA, Razavi M, et al: Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males. Mol Ther. 4:586–592. 2001.PubMed/NCBI View Article : Google Scholar

76 

Favaro P, Downey HD, Zhou JS, Wright JF, Hauck B, Mingozzi F, High KA and Arruda VR: Host and vector-dependent effects on the risk of germline transmission of AAV vectors. Mol Ther. 17:1022–1030. 2009.PubMed/NCBI View Article : Google Scholar

77 

Food and Drug Administration: Guidance for industry: Gene therapy clinical trials-Observing subjects for delayed adverse events. 2006.

78 

Leebeek FWG, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Castaman G, Seifried E, Schwaeble J, Bönig H, et al: AMT-060 gene therapy in adults with severe or moderate-severe hemophilia B confirm stable FIX expression and durable reductions in bleeding and factor IX consumption for up to 5 years. Blood. 136(26)2020.

79 

Sabatino DE, Lange AM, Altynova ES, Sarkar R, Zhou S, Merricks EP, Franck HG, Nichols TC, Arruda VR and Kazazian HH Jr: Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors. Mol Ther. 19:442–449. 2011.PubMed/NCBI View Article : Google Scholar

80 

Gollomp KL, Doshi BS and Arruda VR: Gene therapy for hemophilia: Progress to date and challenges moving forward. Transfus Apher Sci. 58:602–612. 2019.PubMed/NCBI View Article : Google Scholar

81 

Samori Z and Badran I: Somatic gene therapy: Ethical consideration and Islamic Fiqhi perspective. J Engineering and Applied Sciences. 13:4353–4561. 2018.

82 

Bolous NS, Chen Y, Wang H, Davidoff AM, Devidas M, Jacobs TW, Meagher MM, Nathwani AC, Neufeld EJ, Piras BA, et al: The cost-effectiveness of gene therapy for severe hemophilia B: A microsimulation study from the United States perspective. Blood. 138:1677–1690. 2021.PubMed/NCBI View Article : Google Scholar

83 

Reiss UM, Zhang L and Ohmori T: Hemophilia gene therapy-New country initiatives. Haemophilia. 27:132–141. 2021.PubMed/NCBI View Article : Google Scholar

84 

Goodman C, Berntorp E and Wong O: International Haemophilia Access Strategy Council. Alternative payment models for durable and potentially curative therapies: The case of gene therapy for haemophilia A. Haemophilia. 28:27–34. 2022.PubMed/NCBI View Article : Google Scholar

85 

Sharma A, Mathew ME, Sriganesh V and Reiss UM: Gene therapy for haemophilia. Cochrane Database Syst Rev. 12(CD010822)2016.PubMed/NCBI View Article : Google Scholar

86 

Drummond MF, Neumann PJ, Sullivan SD, Fricke FU, Tunis S, Dabbous O and Toumi M: Analytic considerations in applying a general economic evaluation reference case to gene therapy. Value Health. 22:661–668. 2019.PubMed/NCBI View Article : Google Scholar

87 

Peyvandi F, Garagiola I and Young G: The past and future of haemophilia: Diagnosis, treatments, and its complications. Lancet. 388:187–197. 2016.PubMed/NCBI View Article : Google Scholar

88 

Pierce GF and Coffin D: Members of the WFH Gene Therapy Round Table Program Committee and Organizing Committee. The 1st WFH gene therapy round table: Understanding the landscape and challenges of gene therapy for haemophilia around the world. Haemophilia. 25:189–194. 2019.PubMed/NCBI View Article : Google Scholar

89 

Doshi BS and Arruda VR: Gene therapy for hemophilia: What does the future hold? Ther Adv Hematol. 9:273–293. 2018.PubMed/NCBI View Article : Google Scholar

90 

George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, Cuker A, Sullivan LM, Majumdar S, Teitel J, et al: Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 377:2215–2227. 2017.PubMed/NCBI View Article : Google Scholar

91 

Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Tangelder M, Castaman G, Schwäble J, Bonig H, et al: Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 131:1022–1031. 2018.PubMed/NCBI View Article : Google Scholar

92 

George LA, Ragni MV, Rasko JEJ, Raffini LJ, Samelson-Jones BJ, Ozelo M, Hazbon M, Runowski AR, Wellman JA, Wachtel K, et al: Long-Term follow-up of the first in human intravascular delivery of AAV for gene transfer: AAV2-hFIX16 for severe hemophilia B. Mol Ther. 28:2073–2082. 2020.PubMed/NCBI View Article : Google Scholar

93 

Konkle BA, Walsh CE, Escobar MA, Josephson NC, Young G, Von Drygalski A, McPhee SWJ, Samulski RJ, Bilic I, de la Rosa M, et al: BAX 335 hemophilia B gene therapy clinical trial results: Potential impact of CpG sequences on gene expression. Blood. 137:763–774. 2021.PubMed/NCBI View Article : Google Scholar

94 

Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K, Dolan G, Reiss U, Phillips M, Riddell A, et al: Phase 1-2 trial of AAVS3 gene therapy in patients with hemophilia B. N Engl J Med. 387:237–247. 2022.PubMed/NCBI View Article : Google Scholar

95 

Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, et al: Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: A single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 9:e504–e513. 2022.PubMed/NCBI View Article : Google Scholar

96 

Powell JS, Ragni MV, White GC II, Lusher JM, Hillman-Wiseman C, Moon TE, Cole V, Ramanathan-Girish S, Roehl H, Sajjadi N, et al: Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood. 102:2038–2045. 2003.PubMed/NCBI View Article : Google Scholar

97 

Mahlangu J, Kaczmarek R, Von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, et al: Two-Year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N Engl J Med. 388:694–705. 2023.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
Copy and paste a formatted citation
Spandidos Publications style
Ali Abdulnabi M, Al‑Saadi E and Al‑Bayaa I: Gene therapy for hemophilia: Recent developments and challenges (Review). World Acad Sci J 7: 41, 2025.
APA
Ali Abdulnabi, M., Al‑Saadi, E., & Al‑Bayaa, I. (2025). Gene therapy for hemophilia: Recent developments and challenges (Review). World Academy of Sciences Journal, 7, 41. https://doi.org/10.3892/wasj.2025.329
MLA
Ali Abdulnabi, M., Al‑Saadi, E., Al‑Bayaa, I."Gene therapy for hemophilia: Recent developments and challenges (Review)". World Academy of Sciences Journal 7.3 (2025): 41.
Chicago
Ali Abdulnabi, M., Al‑Saadi, E., Al‑Bayaa, I."Gene therapy for hemophilia: Recent developments and challenges (Review)". World Academy of Sciences Journal 7, no. 3 (2025): 41. https://doi.org/10.3892/wasj.2025.329
Copy and paste a formatted citation
x
Spandidos Publications style
Ali Abdulnabi M, Al‑Saadi E and Al‑Bayaa I: Gene therapy for hemophilia: Recent developments and challenges (Review). World Acad Sci J 7: 41, 2025.
APA
Ali Abdulnabi, M., Al‑Saadi, E., & Al‑Bayaa, I. (2025). Gene therapy for hemophilia: Recent developments and challenges (Review). World Academy of Sciences Journal, 7, 41. https://doi.org/10.3892/wasj.2025.329
MLA
Ali Abdulnabi, M., Al‑Saadi, E., Al‑Bayaa, I."Gene therapy for hemophilia: Recent developments and challenges (Review)". World Academy of Sciences Journal 7.3 (2025): 41.
Chicago
Ali Abdulnabi, M., Al‑Saadi, E., Al‑Bayaa, I."Gene therapy for hemophilia: Recent developments and challenges (Review)". World Academy of Sciences Journal 7, no. 3 (2025): 41. https://doi.org/10.3892/wasj.2025.329
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team