机构:[1]Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration, in Central Nervous System, Ministry of Education and Tianjin City, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China[2]Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China研究所北京市神经外科研究所首都医科大学附属天坛医院[3]Department of Pathology, Medical College of Hebei University, Baoding, Hebei 071000, China
RNA is rarely used as a therapeutic target due to its flexible structure and instability. CRISPR-Cas13a is a powerful tool for RNA knockdown, and the potential application of CRISPR-Cas13a in cancer cells should be further studied. In this study, overexpression of LwCasl3a by lentivirus in glioma cells reveals that crRNA-EGFP induces a "collateral effect" after knocking down the target gene in EGFP-expressing cells. EGFRvIII is a unique EGFR mutant subtype in glioma, and the CRISPR-Cas13a system induces death in EGFRvIII-overexpressing glioma cells. Bulk and single-cell RNA sequencing analysis in U87-Cas13a-EGFRvIII cells confirm the collateral effect of the CRISPR-Cas13a system. Furthermore, CRISPR-Cas13a inhibits the formation of glioma intracranial tumors in mice. The results demonstrate the collateral effect of the CRISPR-Cas13a system in cancer cells and the powerful tumor-eliminating potential of this system.
基金:
This work was
supported by the National Key Research and Development Programs
of China (No. 2018YFA0209700), Beijing Tianjin Hebei Basic Research
Cooperation Project (18JCZDJC45500 and H2018201306), and the
Tianjin Municipal Science and Technology Commission Project
(15ZXLCSY00060 and 15ZXJZSY00040).
第一作者机构:[1]Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration, in Central Nervous System, Ministry of Education and Tianjin City, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
共同第一作者:
通讯作者:
通讯机构:[1]Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration, in Central Nervous System, Ministry of Education and Tianjin City, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
推荐引用方式(GB/T 7714):
Wang Qixue,Liu Xing,Zhou Junhu,et al.The CRISPR-Cas13a Gene-Editing System Induces Collateral Cleavage of RNA in Glioma Cells[J].ADVANCED SCIENCE.2019,6(20):-.doi:10.1002/advs.201901299.
APA:
Wang, Qixue,Liu, Xing,Zhou, Junhu,Yang, Chao,Wang, Guangxiu...&Kang, Chunsheng.(2019).The CRISPR-Cas13a Gene-Editing System Induces Collateral Cleavage of RNA in Glioma Cells.ADVANCED SCIENCE,6,(20)
MLA:
Wang, Qixue,et al."The CRISPR-Cas13a Gene-Editing System Induces Collateral Cleavage of RNA in Glioma Cells".ADVANCED SCIENCE 6..20(2019):-