CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer
Abstract Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile,...
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-08-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00970-w |
| _version_ | 1818002430491623424 |
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| author | Xianhuang Li Mingming Guo Bei Hou Bin Zheng Zhiyun Wang Mengqian Huang Yanan Xu Jin Chang Tao Wang |
| author_facet | Xianhuang Li Mingming Guo Bei Hou Bin Zheng Zhiyun Wang Mengqian Huang Yanan Xu Jin Chang Tao Wang |
| author_sort | Xianhuang Li |
| collection | DOAJ |
| description | Abstract Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes. |
| first_indexed | 2024-04-14T03:45:50Z |
| format | Article |
| id | doaj.art-2861a474ee9a4e3286ea91a1518ad78d |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T03:45:50Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-2861a474ee9a4e3286ea91a1518ad78d2022-12-22T02:14:15ZengBMCJournal of Nanobiotechnology1477-31552021-08-0119111310.1186/s12951-021-00970-wCRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancerXianhuang Li0Mingming Guo1Bei Hou2Bin Zheng3Zhiyun Wang4Mengqian Huang5Yanan Xu6Jin Chang7Tao Wang8School of Life Sciences, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversitySchool of Life Sciences, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin Key Laboratory of Brain Science and Neural Engineering, Xincheng Hospital of Tianjin University, Tianjin UniversitySchool of Environmental Science and Engineering, Tianjin UniversitySchool of Life Sciences, Tianjin UniversitySchool of Life Sciences, Tianjin UniversitySchool of Life Sciences, Tianjin UniversitySchool of Life Sciences, Tianjin UniversityAbstract Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes.https://doi.org/10.1186/s12951-021-00970-wDrug resistanceCRISPR/Cas9NanoeditorOncogene deletionCervical cancer |
| spellingShingle | Xianhuang Li Mingming Guo Bei Hou Bin Zheng Zhiyun Wang Mengqian Huang Yanan Xu Jin Chang Tao Wang CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer Journal of Nanobiotechnology Drug resistance CRISPR/Cas9 Nanoeditor Oncogene deletion Cervical cancer |
| title | CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer |
| title_full | CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer |
| title_fullStr | CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer |
| title_full_unstemmed | CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer |
| title_short | CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer |
| title_sort | crispr cas9 nanoeditor of double knockout large fragments of e6 and e7 oncogenes for reversing drugs resistance in cervical cancer |
| topic | Drug resistance CRISPR/Cas9 Nanoeditor Oncogene deletion Cervical cancer |
| url | https://doi.org/10.1186/s12951-021-00970-w |
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