Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade
Abstract Glioblastoma (GBM) is a primary brain tumor known for its high levels of aggressiveness and resistance to current treatments such as radiotherapy and chemotherapy. As a result, there is a pressing need for innovative therapeutic approaches to combat GBM. Thus, we have developed an engineere...
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| Language: | English |
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03112-8 |
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| author | Xiaolin Liu Xiao Liu Xiaonan Luo Maorong Zhu Nannan Liu Juan Li Qi Zhang Cheng Zou Yuxin Wu Zhengcong Cao Shuangxin Ma Weizhong Wang Guangzhao Yang Jintao Gu Wei Liu Meng Li Anan Yin Yalong He Wei Lin |
| author_facet | Xiaolin Liu Xiao Liu Xiaonan Luo Maorong Zhu Nannan Liu Juan Li Qi Zhang Cheng Zou Yuxin Wu Zhengcong Cao Shuangxin Ma Weizhong Wang Guangzhao Yang Jintao Gu Wei Liu Meng Li Anan Yin Yalong He Wei Lin |
| author_sort | Xiaolin Liu |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is a primary brain tumor known for its high levels of aggressiveness and resistance to current treatments such as radiotherapy and chemotherapy. As a result, there is a pressing need for innovative therapeutic approaches to combat GBM. Thus, we have developed an engineered multifunctional extracellular vesicle (EV) delivery system that offers an "all-in-one" strategy for GBM therapy. Our approach involved the use of genetic engineering to the long-lasting production of PD-1 and the brain-specific peptide angiopep-2 on the surface of EVs. These modified EVs were then utilized to rejuvenate exhausted CD8+ T cells blocking PD-L1, resulting in significant therapeutic benefits for GBM treatment. Furthermore, the EVs contained Cas9 protein and sgRNA for precise and minimally invasive gene therapy, which addressing the key barriers associated with in vivo CRISPR‒Cas9 gene editing treatment. The multigene editing of EVs resulted in efficient intratumor multisite gene editing (PLK1: 58.6%, VEGF: 52.7%), leading to the successful apoptosis of tumor cells in vivo and demonstrating an antiangiogenic effect. This research introduces a promising universal platform for combining immune checkpoint blockade therapy with gene editing treatment. Graphical Abstract |
| format | Article |
| id | doaj-art-489774aae2774a51aa3ea9b60c6d23d2 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-489774aae2774a51aa3ea9b60c6d23d22025-02-09T12:53:10ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111810.1186/s12951-025-03112-8Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockadeXiaolin Liu0Xiao Liu1Xiaonan Luo2Maorong Zhu3Nannan Liu4Juan Li5Qi Zhang6Cheng Zou7Yuxin Wu8Zhengcong Cao9Shuangxin Ma10Weizhong Wang11Guangzhao Yang12Jintao Gu13Wei Liu14Meng Li15Anan Yin16Yalong He17Wei Lin18State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing HospitalSchool of Basic Medicine, The Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityDepartment of Plastic and Reconstructive Surgery, Xijing HospitalDepartment of Neurosurgery, Xijing HospitalDepartment of Neurosurgery, Xijing HospitalState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing HospitalDepartment of Neurosurgery, Xijing HospitalState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing HospitalState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical UniversityDepartment of Plastic and Reconstructive Surgery, Xijing HospitalDepartment of Neurosurgery, Xijing HospitalDepartment of Neurosurgery, Xijing HospitalAbstract Glioblastoma (GBM) is a primary brain tumor known for its high levels of aggressiveness and resistance to current treatments such as radiotherapy and chemotherapy. As a result, there is a pressing need for innovative therapeutic approaches to combat GBM. Thus, we have developed an engineered multifunctional extracellular vesicle (EV) delivery system that offers an "all-in-one" strategy for GBM therapy. Our approach involved the use of genetic engineering to the long-lasting production of PD-1 and the brain-specific peptide angiopep-2 on the surface of EVs. These modified EVs were then utilized to rejuvenate exhausted CD8+ T cells blocking PD-L1, resulting in significant therapeutic benefits for GBM treatment. Furthermore, the EVs contained Cas9 protein and sgRNA for precise and minimally invasive gene therapy, which addressing the key barriers associated with in vivo CRISPR‒Cas9 gene editing treatment. The multigene editing of EVs resulted in efficient intratumor multisite gene editing (PLK1: 58.6%, VEGF: 52.7%), leading to the successful apoptosis of tumor cells in vivo and demonstrating an antiangiogenic effect. This research introduces a promising universal platform for combining immune checkpoint blockade therapy with gene editing treatment. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03112-8GlioblastomaImmunotherapyCRISPR/Cas9Gene editingAll-in-one |
| spellingShingle | Xiaolin Liu Xiao Liu Xiaonan Luo Maorong Zhu Nannan Liu Juan Li Qi Zhang Cheng Zou Yuxin Wu Zhengcong Cao Shuangxin Ma Weizhong Wang Guangzhao Yang Jintao Gu Wei Liu Meng Li Anan Yin Yalong He Wei Lin Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade Journal of Nanobiotechnology Glioblastoma Immunotherapy CRISPR/Cas9 Gene editing All-in-one |
| title | Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade |
| title_full | Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade |
| title_fullStr | Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade |
| title_full_unstemmed | Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade |
| title_short | Synergistic strategies for glioblastoma treatment: CRISPR-based multigene editing combined with immune checkpoint blockade |
| title_sort | synergistic strategies for glioblastoma treatment crispr based multigene editing combined with immune checkpoint blockade |
| topic | Glioblastoma Immunotherapy CRISPR/Cas9 Gene editing All-in-one |
| url | https://doi.org/10.1186/s12951-025-03112-8 |
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