Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.
Central Nervous system tumors
Zika virus
cancer stem cell
glioblastoma
medulloblastoma
miRNA-sensitive oncolytic virus
virus genetic engineering
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:
10 Jan 2024
10 Jan 2024
Historique:
received:
06
06
2023
revised:
09
10
2023
accepted:
05
01
2024
medline:
12
1
2024
pubmed:
12
1
2024
entrez:
12
1
2024
Statut:
aheadofprint
Résumé
Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: firstly, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors - highly deadly diseases in urgent need of effective advanced therapies.
Identifiants
pubmed: 38213031
pii: S1525-0016(24)00006-6
doi: 10.1016/j.ymthe.2024.01.006
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.