Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.
Mol Ther
; 32(2): 440-456, 2024 Feb 07.
Article
in En
| MEDLINE
| ID: mdl-38213031
ABSTRACT
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 first, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Central Nervous System Neoplasms
/
MicroRNAs
/
Oncolytic Viruses
/
Oncolytic Virotherapy
/
Zika Virus
/
Zika Virus Infection
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Ther
/
Mol. ther
/
Molecular therapy
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2024
Type:
Article
Affiliation country:
Brazil