Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos
IntroductionDue 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...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491230/full |
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| author | Mengwei Niu Wenyanbo Yi Zhuofan Dong Xiaofeng Li Xue Dong Lifang Yu Yao Han Oujia Zhang Ziyang Sheng Jing An Hao Li Yansong Sun |
| author_facet | Mengwei Niu Wenyanbo Yi Zhuofan Dong Xiaofeng Li Xue Dong Lifang Yu Yao Han Oujia Zhang Ziyang Sheng Jing An Hao Li Yansong Sun |
| author_sort | Mengwei Niu |
| collection | DOAJ |
| description | IntroductionDue 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.MethodIn 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.ResultsWe found that the vivo-3′UTR molecule targeting the 3′ untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3′UTR 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 μM of vivo-3′UTR 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′UTR had a notable preventive effect against viral infection.ConclusionThis 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. |
| format | Article |
| id | doaj-art-c856e69bd7fe4bf0989eb2582e97a6d9 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c856e69bd7fe4bf0989eb2582e97a6d92024-11-29T05:10:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14912301491230Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-MorpholinosMengwei Niu0Wenyanbo Yi1Zhuofan Dong2Xiaofeng Li3Xue Dong4Lifang Yu5Yao Han6Oujia Zhang7Ziyang Sheng8Jing An9Hao Li10Yansong Sun11State Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, ChinaIntroductionDue 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.MethodIn 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.ResultsWe found that the vivo-3′UTR molecule targeting the 3′ untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3′UTR 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 μM of vivo-3′UTR 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′UTR had a notable preventive effect against viral infection.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491230/fullantisense oligonucleotidesantiviraldengue virus (DENV)antisense therapynucleic acid therapy |
| spellingShingle | Mengwei Niu Wenyanbo Yi Zhuofan Dong Xiaofeng Li Xue Dong Lifang Yu Yao Han Oujia Zhang Ziyang Sheng Jing An Hao Li Yansong Sun Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos Frontiers in Immunology antisense oligonucleotides antiviral dengue virus (DENV) antisense therapy nucleic acid therapy |
| title | Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos |
| title_full | Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos |
| title_fullStr | Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos |
| title_full_unstemmed | Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos |
| title_short | Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos |
| title_sort | effective inhibition of dengue virus replication using 3 utr targeted vivo morpholinos |
| topic | antisense oligonucleotides antiviral dengue virus (DENV) antisense therapy nucleic acid therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491230/full |
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