Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps
Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this appro...
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003686 |
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| author | Wolfgang Miesbach Paul Batty Pratima Chowdary Sylvia Fong Radoslaw Kaczmarek Frank W.G. Leebeek Brian Long Johnny Mahlangu Mike Makris Glenn F. Pierce Steven W. Pipe Alok Srivastava Jan Voorberg Flora Peyvandi |
| author_facet | Wolfgang Miesbach Paul Batty Pratima Chowdary Sylvia Fong Radoslaw Kaczmarek Frank W.G. Leebeek Brian Long Johnny Mahlangu Mike Makris Glenn F. Pierce Steven W. Pipe Alok Srivastava Jan Voorberg Flora Peyvandi |
| author_sort | Wolfgang Miesbach |
| collection | DOAJ |
| description | Adeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation. This manuscript follows literature reviews and structured discussions by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Working Group on Gene Therapy that identified specific areas requiring standardization of methods, including viral vector production, liver function assessment, quantification of factor (F)VIII and FIX expression levels, assessment of antiadeno-associated viral antibodies, and genomic integration detection methods. Standardization strategies aim to achieve consistent vector quality, effective patient selection, and uniform assessment methods by implementing advanced laboratory techniques and standardized protocols. Standardizing these parameters is essential for improving the understanding of short-term and long-term safety and efficacy of gene therapy in hemophilia. This effort aims to enhance the predictability of individual responses, address variability in outcomes, and ultimately provide more effective, safer, and personalized treatment options for individuals with hemophilia. |
| format | Article |
| id | doaj-art-9f81ba758a8d4188a5732672d6cc3cf7 |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-9f81ba758a8d4188a5732672d6cc3cf72025-01-20T04:17:48ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102673Adeno-associated virus-based gene therapy for hemophilia–addressing the gapsWolfgang Miesbach0Paul Batty1Pratima Chowdary2Sylvia Fong3Radoslaw Kaczmarek4Frank W.G. Leebeek5Brian Long6Johnny Mahlangu7Mike Makris8Glenn F. Pierce9Steven W. Pipe10Alok Srivastava11Jan Voorberg12Flora Peyvandi13Medical Clinic 2, University Hospital Frankfurt, Frankfurt, Germany; Correspondence Wolfgang Miesbach, Medical Clinic 2, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.Department of Haematology, Cancer Institute, University College London, London, United Kingdom; Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, United KingdomKatharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, United KingdomQueen’s University, Kingston, Ontario, CanadaHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA; Ludwik Hirszfeld Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Wroclaw, PolandDepartment of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands4D Molecular Therapeutics, Emeryville, California, USADepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaSchool of Medicine and Population Health, University of Sheffield, Sheffield, United KingdomWorf Federation of Hemophilia, Montreal, Québec, CanadaUniversity of Michigan, Ann Arbor, Michigan, USASt. John’s Research Institute, St. John’s Medical College Hospital, Bengaluru, IndiaSanquin Research, Amsterdam, the NetherlandsFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, ItalyAdeno-associated virus-based gene therapy for hemophilia has emerged as a revolutionary treatment option, offering potential correction of clotting factor deficiency through a single intravenous infusion of functional genes directed to hepatocytes. With 3 gene therapies recently approved, this approach shows promise in transforming the lives of individuals with hemophilia. However, the complexity of gene therapy and the lack of standardization of methods in different components of this therapy can lead to unique challenges for clinical implementation. This manuscript follows literature reviews and structured discussions by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Working Group on Gene Therapy that identified specific areas requiring standardization of methods, including viral vector production, liver function assessment, quantification of factor (F)VIII and FIX expression levels, assessment of antiadeno-associated viral antibodies, and genomic integration detection methods. Standardization strategies aim to achieve consistent vector quality, effective patient selection, and uniform assessment methods by implementing advanced laboratory techniques and standardized protocols. Standardizing these parameters is essential for improving the understanding of short-term and long-term safety and efficacy of gene therapy in hemophilia. This effort aims to enhance the predictability of individual responses, address variability in outcomes, and ultimately provide more effective, safer, and personalized treatment options for individuals with hemophilia.http://www.sciencedirect.com/science/article/pii/S2475037924003686gene therapyhemophiliamethodssafetystandardization |
| spellingShingle | Wolfgang Miesbach Paul Batty Pratima Chowdary Sylvia Fong Radoslaw Kaczmarek Frank W.G. Leebeek Brian Long Johnny Mahlangu Mike Makris Glenn F. Pierce Steven W. Pipe Alok Srivastava Jan Voorberg Flora Peyvandi Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps Research and Practice in Thrombosis and Haemostasis gene therapy hemophilia methods safety standardization |
| title | Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps |
| title_full | Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps |
| title_fullStr | Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps |
| title_full_unstemmed | Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps |
| title_short | Adeno-associated virus-based gene therapy for hemophilia–addressing the gaps |
| title_sort | adeno associated virus based gene therapy for hemophilia addressing the gaps |
| topic | gene therapy hemophilia methods safety standardization |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003686 |
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