Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.
adeno-associated virus
clinical trials
gene therapy
promoters
tropism
Journal
Frontiers in medicine
ISSN: 2296-858X
Titre abrégé: Front Med (Lausanne)
Pays: Switzerland
ID NLM: 101648047
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
11
2021
accepted:
06
12
2021
entrez:
28
2
2022
pubmed:
1
3
2022
medline:
1
3
2022
Statut:
epublish
Résumé
Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene packaging capacities, off-target transduction, and immunogenicity. In this study, we analysed over two decades of AAV applications, in 136 clinical trials. This meta-analysis aims to provide an up-to-date overview of the use and successes of AAVs in clinical trials, while evaluating the approaches used to address the above challenges. First, this study reveals that the speed of novel AAV development has varied between therapeutic areas, with particular room for improvement in Central Nervous System disorders, where development has been slow. Second, the lack of dose-dependent toxicity and efficacy data indicates that optimal dosing regimes remain elusive. Third, more clinical data on the effectiveness of various immune-modulation strategies and gene editing approaches are required to direct future research and to accelerate the translation of AAV-mediated gene therapy into human applications.
Identifiants
pubmed: 35223884
doi: 10.3389/fmed.2021.809118
pmc: PMC8864161
doi:
Types de publication
Systematic Review
Langues
eng
Pagination
809118Subventions
Organisme : Medical Research Council
ID : MC_PC_17162
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Au, Isalan and Mielcarek.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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