Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors
Abstract Current cancer gene therapies rely primarily on antitumor immunity, but the exploration of alternative mRNA cargoes for direct antitumor effects is crucial to expand cancer gene therapies. Here we show that lipid nanoparticles (LNPs) carrying mRNA encoding a viral 3 C protease can efficient...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59440-8 |
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| author | Xiaotong Yang Wei Li Shaokang Yang Zhuang Wang Jiye Yin Wenhao Zhang Huimin Tao Siqi Li Xiaojia Guo Qingsong Dai Weiyan Zhu Yuexiang Li Xintong Yan Chongda Luo Jiazheng Li Sichen Ren Ping Wang Yunfeng Shao Yan Luo Zhenyang Li Jingjing Yang Zhijie Chang Ruiyuan Cao Song Li Wu Zhong |
| author_facet | Xiaotong Yang Wei Li Shaokang Yang Zhuang Wang Jiye Yin Wenhao Zhang Huimin Tao Siqi Li Xiaojia Guo Qingsong Dai Weiyan Zhu Yuexiang Li Xintong Yan Chongda Luo Jiazheng Li Sichen Ren Ping Wang Yunfeng Shao Yan Luo Zhenyang Li Jingjing Yang Zhijie Chang Ruiyuan Cao Song Li Wu Zhong |
| author_sort | Xiaotong Yang |
| collection | DOAJ |
| description | Abstract Current cancer gene therapies rely primarily on antitumor immunity, but the exploration of alternative mRNA cargoes for direct antitumor effects is crucial to expand cancer gene therapies. Here we show that lipid nanoparticles (LNPs) carrying mRNA encoding a viral 3 C protease can efficiently suppress tumors by selectively inducing tumor cell apoptosis. In various solid tumor models, intracranial injection of LNPs carrying mRNA encoding the 3 C protease (3C-LNPs) significantly inhibits tumor growth and prolongs survival in glioblastoma models. Similarly, subcutaneous injection reduces tumor volume and inhibits angiogenesis in a breast cancer model, while intravenous injection inhibits tumor growth and angiogenesis and prolongs survival in hepatocellular carcinoma models. Mass spectrometry and cleavage site prediction assays identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as the main target degraded by the 3 C protease. This study suggests that viral protease mRNA could be a promising broad-spectrum antitumor therapeutic. |
| format | Article |
| id | doaj-art-c7139cedd0f7406387d0d2f984af4604 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c7139cedd0f7406387d0d2f984af46042025-08-20T01:49:39ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59440-8Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid TumorsXiaotong Yang0Wei Li1Shaokang Yang2Zhuang Wang3Jiye Yin4Wenhao Zhang5Huimin Tao6Siqi Li7Xiaojia Guo8Qingsong Dai9Weiyan Zhu10Yuexiang Li11Xintong Yan12Chongda Luo13Jiazheng Li14Sichen Ren15Ping Wang16Yunfeng Shao17Yan Luo18Zhenyang Li19Jingjing Yang20Zhijie Chang21Ruiyuan Cao22Song Li23Wu Zhong24National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and ToxicologyNational Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologySchool of Basic Medical Sciences, Tsinghua UniversityNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and ToxicologyAbstract Current cancer gene therapies rely primarily on antitumor immunity, but the exploration of alternative mRNA cargoes for direct antitumor effects is crucial to expand cancer gene therapies. Here we show that lipid nanoparticles (LNPs) carrying mRNA encoding a viral 3 C protease can efficiently suppress tumors by selectively inducing tumor cell apoptosis. In various solid tumor models, intracranial injection of LNPs carrying mRNA encoding the 3 C protease (3C-LNPs) significantly inhibits tumor growth and prolongs survival in glioblastoma models. Similarly, subcutaneous injection reduces tumor volume and inhibits angiogenesis in a breast cancer model, while intravenous injection inhibits tumor growth and angiogenesis and prolongs survival in hepatocellular carcinoma models. Mass spectrometry and cleavage site prediction assays identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as the main target degraded by the 3 C protease. This study suggests that viral protease mRNA could be a promising broad-spectrum antitumor therapeutic.https://doi.org/10.1038/s41467-025-59440-8 |
| spellingShingle | Xiaotong Yang Wei Li Shaokang Yang Zhuang Wang Jiye Yin Wenhao Zhang Huimin Tao Siqi Li Xiaojia Guo Qingsong Dai Weiyan Zhu Yuexiang Li Xintong Yan Chongda Luo Jiazheng Li Sichen Ren Ping Wang Yunfeng Shao Yan Luo Zhenyang Li Jingjing Yang Zhijie Chang Ruiyuan Cao Song Li Wu Zhong Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors Nature Communications |
| title | Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors |
| title_full | Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors |
| title_fullStr | Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors |
| title_full_unstemmed | Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors |
| title_short | Gene Therapy with Enterovirus 3 C Protease: A Promising Strategy for Various Solid Tumors |
| title_sort | gene therapy with enterovirus 3 c protease a promising strategy for various solid tumors |
| url | https://doi.org/10.1038/s41467-025-59440-8 |
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