Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool
Abstract Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISP...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202206517 |
| _version_ | 1827972768465944576 |
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| author | Tianwen Li Liansheng Zhang Tao Lu Tongming Zhu Canbin Feng Ni Gao Fei Liu Jingyu Yu Kezhu Chen Junjie Zhong Qisheng Tang Quan Zhang Xiangyang Deng Junwei Ren Jun Zeng Haibo Zhou Jianhong Zhu |
| author_facet | Tianwen Li Liansheng Zhang Tao Lu Tongming Zhu Canbin Feng Ni Gao Fei Liu Jingyu Yu Kezhu Chen Junjie Zhong Qisheng Tang Quan Zhang Xiangyang Deng Junwei Ren Jun Zeng Haibo Zhou Jianhong Zhu |
| author_sort | Tianwen Li |
| collection | DOAJ |
| description | Abstract Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide‐optimized and EVs‐delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)‐triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short‐acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases. |
| first_indexed | 2024-04-09T19:26:35Z |
| format | Article |
| id | doaj.art-5e4782dfb31142b0b3ff70abf43f2c66 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-09T19:26:35Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-5e4782dfb31142b0b3ff70abf43f2c662023-04-05T08:09:48ZengWileyAdvanced Science2198-38442023-04-011010n/an/a10.1002/advs.202206517Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing ToolTianwen Li0Liansheng Zhang1Tao Lu2Tongming Zhu3Canbin Feng4Ni Gao5Fei Liu6Jingyu Yu7Kezhu Chen8Junjie Zhong9Qisheng Tang10Quan Zhang11Xiangyang Deng12Junwei Ren13Jun Zeng14Haibo Zhou15Jianhong Zhu16Department of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaInstitute of Neuroscience State Key Laboratory of Neuroscience Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Research Center for Brain Science and Brain‐Inspired Intelligence Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaInstitute of Neuroscience State Key Laboratory of Neuroscience Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Research Center for Brain Science and Brain‐Inspired Intelligence Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaInstitute of Neuroscience State Key Laboratory of Neuroscience Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Research Center for Brain Science and Brain‐Inspired Intelligence Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaInstitute of Neuroscience State Key Laboratory of Neuroscience Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Research Center for Brain Science and Brain‐Inspired Intelligence Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaAnhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease Molecular Diagnosis Center Department of Pulmonary and Critical Care Medicine First Affiliated Hospital Bengbu Medical College No. 287 Changhuai Road Bengbu Anhui 233004 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaInstitute of Neuroscience State Key Laboratory of Neuroscience Key Laboratory of Primate Neurobiology CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Research Center for Brain Science and Brain‐Inspired Intelligence Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 ChinaDepartment of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders National Key Laboratory for Medical Neurobiology Institutes of Brain Science Shanghai Key Laboratory of Brain Function and Regeneration Institute of Neurosurgery MOE Frontiers Center for Brain Science Shanghai 200040 ChinaAbstract Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide‐optimized and EVs‐delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)‐triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short‐acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.https://doi.org/10.1002/advs.202206517CRISPR/CasRxextracellular vesiclesinflammatory diseaseRNA editing |
| spellingShingle | Tianwen Li Liansheng Zhang Tao Lu Tongming Zhu Canbin Feng Ni Gao Fei Liu Jingyu Yu Kezhu Chen Junjie Zhong Qisheng Tang Quan Zhang Xiangyang Deng Junwei Ren Jun Zeng Haibo Zhou Jianhong Zhu Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool Advanced Science CRISPR/CasRx extracellular vesicles inflammatory disease RNA editing |
| title | Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool |
| title_full | Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool |
| title_fullStr | Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool |
| title_full_unstemmed | Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool |
| title_short | Engineered Extracellular Vesicle‐Delivered CRISPR/CasRx as a Novel RNA Editing Tool |
| title_sort | engineered extracellular vesicle delivered crispr casrx as a novel rna editing tool |
| topic | CRISPR/CasRx extracellular vesicles inflammatory disease RNA editing |
| url | https://doi.org/10.1002/advs.202206517 |
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