{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:39:04Z","timestamp":1779251944125,"version":"3.51.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Due to the impact of antibody-dependent enhancement and viral variation, effective vaccines or antiviral therapies remain lacking for the dengue virus (DENV). Nucleic acid drugs, particularly Vivo-Morpholinos (MOs), have emerged as a promising avenue for antiviral treatment due to their programmability and precise targeting, as well as their safety and stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this study, we designed and developed 10 morpho-modified (octa-guanidine dendrimer) vivo-MO molecules that target each coding gene of DENV. Subsequently, we assessed the inhibitory impact of vivo-MOs on dengue viral RNA load utilizing qRT-PCR. Furthermore, we examined the inhibitory effect on the live virus through a plaque assay and the TCID50 assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the vivo-3\u2032UTR molecule targeting the 3\u2032 untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3\u2032UTR demonstrated 99% inhibition of dengue virus RNA and the inhibition of up to 98% of the live virus. Additionally, the targeted sequence was conserved among all four DENV serotypes, and treatment with 10 \u03bcM of vivo-3\u2032UTR resulted in a reduction of viral titers for all four DENV serotypes by over 99.99%. Additionally, we revealed that pre-treatment with vivo-3\u2032UTR had a notable preventive effect against viral infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study screened an effective vivo-MO target drug for the treatment of dengue virus infection, demonstrating low toxicity in mammalian cell lines, and proposed a novel preventive antiviral approach.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1491230","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T05:14:40Z","timestamp":1732857280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effective inhibition of dengue virus replication using 3\u2032UTR-targeted 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