A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection
Abstract To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad‐spectrum targeting of influenza A virus (IAV) from human, avian...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202414651 |
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| author | Zhuanli Wu Chengcheng Zhao Hui Ai Zhen Wang Mingyue Chen Yanli Lyu Qi Tong Litao Liu Honglei Sun Juan Pu Ran Zhang Xiaoxiang Hu Jinhua Liu Xiaowei Ma Yipeng Sun |
| author_facet | Zhuanli Wu Chengcheng Zhao Hui Ai Zhen Wang Mingyue Chen Yanli Lyu Qi Tong Litao Liu Honglei Sun Juan Pu Ran Zhang Xiaoxiang Hu Jinhua Liu Xiaowei Ma Yipeng Sun |
| author_sort | Zhuanli Wu |
| collection | DOAJ |
| description | Abstract To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad‐spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors. The SCSD system can precisely deliver an all‐RNA‐based CRISPR/Cas13d system into potentially infected cells. This drug is shown to reduce the viral load in the lungs by 2.37 log10 TCID50 mL−1 and protect 100% of mice from lethal influenza infection. The SCSD‐based CRISPR/Cas13d system shows promise for the flexible and efficient therapy of infections caused by rapidly evolving and novel viruses. |
| format | Article |
| id | doaj-art-b5728baaae324d3097ac9e17f037aee4 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b5728baaae324d3097ac9e17f037aee42025-08-20T03:32:24ZengWileyAdvanced Science2198-38442025-03-01129n/an/a10.1002/advs.202414651A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza InfectionZhuanli Wu0Chengcheng Zhao1Hui Ai2Zhen Wang3Mingyue Chen4Yanli Lyu5Qi Tong6Litao Liu7Honglei Sun8Juan Pu9Ran Zhang10Xiaoxiang Hu11Jinhua Liu12Xiaowei Ma13Yipeng Sun14National Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaState Key Laboratory of Animal Biotech Breeding College of Biological Sciences China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaNational Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 ChinaAbstract To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad‐spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors. The SCSD system can precisely deliver an all‐RNA‐based CRISPR/Cas13d system into potentially infected cells. This drug is shown to reduce the viral load in the lungs by 2.37 log10 TCID50 mL−1 and protect 100% of mice from lethal influenza infection. The SCSD‐based CRISPR/Cas13d system shows promise for the flexible and efficient therapy of infections caused by rapidly evolving and novel viruses.https://doi.org/10.1002/advs.202414651Cas13d mRNAinfluenza virusessusceptible cell‐selective delivery |
| spellingShingle | Zhuanli Wu Chengcheng Zhao Hui Ai Zhen Wang Mingyue Chen Yanli Lyu Qi Tong Litao Liu Honglei Sun Juan Pu Ran Zhang Xiaoxiang Hu Jinhua Liu Xiaowei Ma Yipeng Sun A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection Advanced Science Cas13d mRNA influenza viruses susceptible cell‐selective delivery |
| title | A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection |
| title_full | A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection |
| title_fullStr | A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection |
| title_full_unstemmed | A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection |
| title_short | A Susceptible Cell‐Selective Delivery (SCSD) of mRNA‐Encoded Cas13d Against Influenza Infection |
| title_sort | susceptible cell selective delivery scsd of mrna encoded cas13d against influenza infection |
| topic | Cas13d mRNA influenza viruses susceptible cell‐selective delivery |
| url | https://doi.org/10.1002/advs.202414651 |
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