Lethal immunotoxicity in high-dose systemic AAV therapy.
AAV
ARDS
CRISPR
DMD
Duchenne muscular dystrophy
acute respiratory distress syndrome
adeno-associated virus
death
immunotoxicity
innate immune response
systemic gene therapy
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
received:
07
10
2023
revised:
09
10
2023
accepted:
09
10
2023
pmc-release:
01
11
2024
medline:
6
11
2023
pubmed:
12
10
2023
entrez:
12
10
2023
Statut:
ppublish
Résumé
High-dose systemic gene therapy with adeno-associated virus (AAV) is in clinical trials to treat various inherited diseases. Despite remarkable success in spinal muscular atrophy and promising results in other diseases, fatality has been observed due to liver, kidney, heart, or lung failure. Innate and adaptive immune responses to the vector play a critical role in the toxicity. Host factors also contribute to patient death. This mini-review summarizes clinical findings and calls for concerted efforts from all stakeholders to better understand the mechanisms underlying lethality in AAV gene therapy and to develop effective strategies to prevent/treat high-dose systemic AAV-gene-therapy-induced immunotoxicity.
Identifiants
pubmed: 37822079
pii: S1525-0016(23)00556-7
doi: 10.1016/j.ymthe.2023.10.015
pmc: PMC10638066
pii:
doi:
Substances chimiques
Dystrophin
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3123-3126Subventions
Organisme : NIAMS NIH HHS
ID : R21 AR081018
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS090634
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI177600
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070517
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS131416
Pays : United States
Informations de copyright
Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.D. is a member of the scientific advisory board for Solid Biosciences and an equity holder of Solid Biosciences, a member of the scientific advisory board for Sardocor Corp., and an inventor of several issued and filed patents on DMD gene therapy and AAV vectors.
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