Combinatorial gene therapy for epilepsy: Gene sequence positioning and AAV serotype influence expression and inhibitory effect on seizures.
Journal
Gene therapy
ISSN: 1476-5462
Titre abrégé: Gene Ther
Pays: England
ID NLM: 9421525
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
03
12
2021
accepted:
16
03
2023
revised:
24
02
2023
medline:
28
8
2023
pubmed:
8
4
2023
entrez:
7
4
2023
Statut:
ppublish
Résumé
Gene therapy with AAV vectors carrying genes for neuropeptide Y and its receptor Y2 has been shown to inhibit seizures in multiple animal models of epilepsy. It is however unknown how the AAV serotype or the sequence order of these two transgenes in the expression cassette affects the actual parenchymal gene expression levels and the seizure-suppressant efficacy. To address these questions, we compared three viral vector serotypes (AAV1, AAV2 and AAV8) and two transgene sequence orders (NPY-IRES-Y2 and Y2-IRES-NPY) in a rat model of acutely induced seizures. Wistar male rats were injected bilaterally with viral vectors and 3 weeks later acute seizures were induced by a subcutaneous injection of kainate. The latency until 1
Identifiants
pubmed: 37029201
doi: 10.1038/s41434-023-00399-w
pii: 10.1038/s41434-023-00399-w
pmc: PMC10457185
doi:
Substances chimiques
Neuropeptide Y
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-658Informations de copyright
© 2023. The Author(s).
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