Hemophilia A/B.
AAV vector
Factor IX
Factor VIII
Gene therapy
Hemophilia
Journal
Hematology/oncology clinics of North America
ISSN: 1558-1977
Titre abrégé: Hematol Oncol Clin North Am
Pays: United States
ID NLM: 8709473
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
pubmed:
1
7
2022
medline:
20
7
2022
entrez:
30
6
2022
Statut:
ppublish
Résumé
Adeno-associated virus (AAV)-mediated gene transfer has successfully raised, and in some cases transiently normalized, FVIII or FIX activity levels in adults with severe hemophilia. Raising FVIII/IX levels, particularly greater than ∼15 IU/dL (mild deficiency), corresponds to a marked decrease in spontaneous and provoked bleeding, dramatic reduction in factor concentrate use, and improved quality of life (QoL). Limited understanding of innate and adaptive immune system responses and hepatocyte transgene expression and stress responses to AAV-mediated gene transfer contribute to the variability in initial and long-term factor protein expression. Lentiviral (LV) and CRISPR/Cas-9 gene therapy approaches may further bolster the range of eligible participants and improve transgene expression and durability.
Identifiants
pubmed: 35773055
pii: S0889-8588(22)00030-2
doi: 10.1016/j.hoc.2022.03.009
pii:
doi:
Substances chimiques
Factor VIII
9001-27-8
Factor IX
9001-28-9
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
797-812Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure S.E. Croteau has served as a consultant for Bayer, BioMarin, CSL-Behring, HEMA Biologics, Pfizer, Sanofi and received institutional research support from Spark Therapeutics.