Duff, Claire;
Alexander, Ian E;
Baruteau, Julien;
(2023)
Gene therapy for Urea Cycle Defects: an update from historical perspectives to future prospects.
Journal of Inherited Metabolic Disease
10.1002/jimd.12609.
(In press).
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Abstract
Urea cycle defects 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 urea cycle defects, improve quality of life and long-term outcome: adenoviral vectors, adeno-associated viral (AAV) vectors, gene editing, genome integration and non-viral technology with messenger RNA (mRNA). In this review, we present a summarised view of this historical path, which include some seminal milestones of the gene therapy's epic. We provide an update about the state of the art of gene therapy technologies for urea cycle defects and the current advantages and pitfalls driving future directions for research and development. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Gene therapy for Urea Cycle Defects: an update from historical perspectives to future prospects |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jimd.12609 |
| Publisher version: | https://doi.org/10.1002/jimd.12609 |
| Language: | English |
| Additional information: | © 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | ammonia, argininaemia, argininosuccinic aciduria, citrullinaemia, ornithine transcarbamylase, Urea cycle, urea cycle defect |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168105 |
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