Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.

Autor: Duff C; Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK., Alexander IE; Gene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, New South Wales, Australia.; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, New South Wales, Australia., Baruteau J; Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, UK.; National Institute of Health Research Great Ormond Street Biomedical Research Centre, London, UK.; Metabolic Medicine Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2024 Jan; Vol. 47 (1), pp. 50-62. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1002/jimd.12609
Abstrakt: Urea cycle defects (UCDs) are severe inherited metabolic diseases with high unmet needs which present a permanent risk of hyperammonaemic decompensation and subsequent acute death or neurological sequelae, when treated with conventional dietetic and medical therapies. Liver transplantation is currently the only curative option, but has the potential to be supplanted by highly effective gene therapy interventions without the attendant need for life-long immunosuppression or limitations imposed by donor liver supply. Over the last three decades, pioneering genetic technologies have been explored to circumvent the consequences of UCDs, improve quality of life and long-term outcomes: adenoviral vectors, adeno-associated viral vectors, gene editing, genome integration and non-viral technology with messenger RNA. In this review, we present a summarised view of this historical path, which includes some seminal milestones of the gene therapy's epic. We provide an update about the state of the art of gene therapy technologies for UCDs and the current advantages and pitfalls driving future directions for research and development.
(© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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