Characterization of an mRNA-Encoded Antibody Against Henipavirus
Nipah and Hendra viruses are lethal zoonotic pathogens with no approved vaccines or therapeutics. mRNA produced via in vitro transcription enables endogenous protein expression and cost reduction. Here, we systematically screened natural and artificial untranslated regions (UTRs) and identified an o...
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MDPI AG
2025-07-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/47/7/519 |
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| author | Zixuan Liu Bingjie Sun Ting Fang Xiaofan Zhao Yi Ren Zhenwei Song Sijun He Jianmin Li Pengfei Fan Changming Yu |
| author_facet | Zixuan Liu Bingjie Sun Ting Fang Xiaofan Zhao Yi Ren Zhenwei Song Sijun He Jianmin Li Pengfei Fan Changming Yu |
| author_sort | Zixuan Liu |
| collection | DOAJ |
| description | Nipah and Hendra viruses are lethal zoonotic pathogens with no approved vaccines or therapeutics. mRNA produced via in vitro transcription enables endogenous protein expression and cost reduction. Here, we systematically screened natural and artificial untranslated regions (UTRs) and identified an optimal combination for expressing henipavirus-neutralizing antibody 1E5. We generated mRNA-1E5 encapsulated in lipid nanoparticles (mRNA-1E5-LNPs). In vitro, mRNA-1E5-LNPs achieved functional antibody expression levels of >1500 ng/mL. In BALB/c mice, intravenous administration of mRNA-1E5-LNPs induced rapid antibody elevation (peak at day 3), without hepatic toxicity or tissue inflammation. We established two Hendra pseudovirus models in biosafety level 2 facilities to evaluate the efficacy of mRNA-1E5-LNPs. Low-dose prophylactic administration effectively blocked entry of the Hendra pseudovirus. Notably, a single 0.5 mg/kg dose of mRNA-1E5-LNPs, stored at 4 °C for two months and administered 7 days prior, provided good protection. Our findings provide a therapeutic strategy for henipaviral infections and a blueprint for the development of mRNA-based antibodies against emerging viruses. |
| format | Article |
| id | doaj-art-75a8a654119d4e5f97f444d33c7c6fc3 |
| institution | Matheson Library |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj-art-75a8a654119d4e5f97f444d33c7c6fc32025-07-25T13:18:41ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-07-0147751910.3390/cimb47070519Characterization of an mRNA-Encoded Antibody Against HenipavirusZixuan Liu0Bingjie Sun1Ting Fang2Xiaofan Zhao3Yi Ren4Zhenwei Song5Sijun He6Jianmin Li7Pengfei Fan8Changming Yu9Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaNipah and Hendra viruses are lethal zoonotic pathogens with no approved vaccines or therapeutics. mRNA produced via in vitro transcription enables endogenous protein expression and cost reduction. Here, we systematically screened natural and artificial untranslated regions (UTRs) and identified an optimal combination for expressing henipavirus-neutralizing antibody 1E5. We generated mRNA-1E5 encapsulated in lipid nanoparticles (mRNA-1E5-LNPs). In vitro, mRNA-1E5-LNPs achieved functional antibody expression levels of >1500 ng/mL. In BALB/c mice, intravenous administration of mRNA-1E5-LNPs induced rapid antibody elevation (peak at day 3), without hepatic toxicity or tissue inflammation. We established two Hendra pseudovirus models in biosafety level 2 facilities to evaluate the efficacy of mRNA-1E5-LNPs. Low-dose prophylactic administration effectively blocked entry of the Hendra pseudovirus. Notably, a single 0.5 mg/kg dose of mRNA-1E5-LNPs, stored at 4 °C for two months and administered 7 days prior, provided good protection. Our findings provide a therapeutic strategy for henipaviral infections and a blueprint for the development of mRNA-based antibodies against emerging viruses.https://www.mdpi.com/1467-3045/47/7/519henipavirusmRNAUTRantibodymouse modelprotection |
| spellingShingle | Zixuan Liu Bingjie Sun Ting Fang Xiaofan Zhao Yi Ren Zhenwei Song Sijun He Jianmin Li Pengfei Fan Changming Yu Characterization of an mRNA-Encoded Antibody Against Henipavirus Current Issues in Molecular Biology henipavirus mRNA UTR antibody mouse model protection |
| title | Characterization of an mRNA-Encoded Antibody Against Henipavirus |
| title_full | Characterization of an mRNA-Encoded Antibody Against Henipavirus |
| title_fullStr | Characterization of an mRNA-Encoded Antibody Against Henipavirus |
| title_full_unstemmed | Characterization of an mRNA-Encoded Antibody Against Henipavirus |
| title_short | Characterization of an mRNA-Encoded Antibody Against Henipavirus |
| title_sort | characterization of an mrna encoded antibody against henipavirus |
| topic | henipavirus mRNA UTR antibody mouse model protection |
| url | https://www.mdpi.com/1467-3045/47/7/519 |
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