ArticleJournal of virology2026
MicroRNA-124-targeted recombinant Zika virus: a dual-functional and safe candidate for vaccination and oncolytic virotherapy.
Article in Journal of virology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
1 citing paper in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zika virus (ZIKV) remains a significant public health threat due to its pronounced neurotropism linked to Congenital Zika Syndrome (CZS). Paradoxically, the same neurotropism also provides a unique opportunity for exploiting ZIKV as an oncolytic agent against malignant brain tumors such as glioma. However, achieving precise control of ZIKV replication in specific cell types or tissues remains a major challenge. Here, we show that the brain-specific and enriched microRNA, miR-124, is highly expressed in neural progenitor cells (NPCs) and neurons, but minimally expressed in glioma stem cells (GSCs) and differentiated glioma stem cells (DGCs). Based on these observations, we engineered a recombinant ZIKV containing a miR-124 target sequence (miR-124T) inserted into the 3' untranslated region (UTR) of the viral genome, generating the virus designated ZIKV-miR124T. ZIKV-miR124T exhibited a significantly attenuated phenotype across multiple mouse models, including adult A129 mice, BALB/c neonates, and pregnant mice. Importantly, in an orthotopic glioma model, ZIKV-miR124T retained potent oncolytic activity while showing a markedly improved safety profile. Viral replication was strictly confined in the tumor region, with a ~1,000-fold reduction in viral load in non-tumoral brain regions compared to the well-established live-attenuated ZIKV (ZIKV-LAV). Furthermore, a single immunization with ZIKV-miR124T conferred effective protection against lethal ZIKV challenge and significantly reduced vertical transmission in pregnant mice. Collectively, our findings establish a strong proof of concept for a rational, miRNA-guided strategy to generate a next-generation ZIKV platform with dual potential as a safe live-attenuated vaccine and a precisely regulated oncolytic virus. IMPORTANCE: This study presents a crucial advancement in controlling the safety and function of neurotropic viruses. We engineered a dual-purpose ZIKV, ZIKV-miR124T, which is regulated by the brain-specific microRNA, miR-124. This design forces the virus to strongly self-suppress in healthy neural tissue, solving a major safety concern for ZIKV-based therapies. ZIKV-miR124T is shown to be a potent oncolytic agent against malignant glioma while also serving as a highly effective, safe live-attenuated vaccine against ZIKV infection, reducing vertical transmission to the fetus. Our work provides a strong demonstration of utilizing microRNA regulation to achieve precise viral tropism and attenuation, offering a valuable, generalizable strategy for the development of safer and more effective viral therapies and vaccines against neurotropic pathogens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.