[en] The emergence of adeno-associated virus (AAV)-based gene therapy has brought hope to patients with severe monogenic disorders. However, immune responses to AAV vectors and transgene products present challenges that require effective immunosuppressive strategies. This systematic review focuses on the immunosuppressive protocols used in 38 clinical trials and 35 real-world studies, considering a range of monogenic diseases, AAV serotypes, and administration routes. The review underscores the need for a deeper understanding of immunosuppressive regimens to enhance the safety and effectiveness of AAV-based gene therapy. Characterizing the immunological responses associated with various gene therapy treatments is crucial for optimizing treatment protocols and ensuring the safety and efficacy of forthcoming gene therapy interventions. Further research and understanding of the impact of immunosuppression on disease, therapy, and route of administration will contribute to the development of more effective and safer gene therapy approaches in the future.
Disciplines :
Pediatrics
Author, co-author :
Vrellaku, Besarte; Department of Paediatrics, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Sethw Hassan, Ilda; Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Howitt, Rebecca; The Queen's College, University of Oxford, Oxford, UK
Webster, Christopher P; Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Harriss, Eli; Bodleian Health Care Libraries, University of Oxford, Oxford, UK
Betts, Corinne; Department of Paediatrics, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Schettini, Jorge; Department of Paediatrics, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Lion, Mattia; Takeda Pharmaceuticals USA, Inc, Cambridge, MA, USA
Mindur, John E; Takeda Pharmaceuticals USA, Inc, Cambridge, MA, USA
Duerr, Michael; Bayer Aktiengesellschaft, CGT&Rare Diseases, Leverkusen, Deutschland
Shaw, Pamela J; Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Kirby, Janine; Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
Azzouz, Mimoun; Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK, Gene Therapy Innovation & Manufacturing Centre (GTIMC), University of Sheffield, Sheffield, UK. Electronic address: m.azzouz@sheffield.ac.uk
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques
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