The CRISPR/Cas9 system is an efficient genome-editing system that has been successfully applied in the field of gene therapy. However, clinical applications of the CRISPR/Cas9 system are limited by the delivery method and safety concerns. Extracellular Vesicles (EVs) can be released from almost every type of cell, and they act as shuttles to convey molecules between cells. Here, we used EVs derived from epithelial cells as a biosafety delivery platform for the CRISPR/Cas9 system and modified the EVs with a chimeric-antigen receptor (CAR) to give them selective tropism to tumors. Compared to normal EVs, CAR-EVs accumulated in cancer tumors rapidly and released the CRISPR/Cas9 system targeting the MYC oncogene efficiently, both in vitro and in vivo. Taken together, the combination of EV and CAR was confirmed to be a novel strategy facilitating the use of natural gene therapy platforms in cancer treatment in this proof-of-concept research.
基金:
National Natural Science Foundation of China [81630006, 81570196]; Hubei Province National Natural Science Foundation [2018ACA140]; Young Scientists Fund of the National Natural Science Foundation of China [81600125]; General Program of National Natural Science Foundation of China [81570197]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Hematol, Tongji Med Coll, 1095 Jie Fang Ave, Wuhan 430030, Hubei, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Xu Qian,Zhang Zheng,Zhao Lei,et al.Tropism-facilitated delivery of CRISPR/Cas9 system with chimeric antigen receptor-extracellular vesicles against B-cell malignancies[J].JOURNAL OF CONTROLLED RELEASE.2020,326:455-467.doi:10.1016/j.jconrel.2020.07.033.
APA:
Xu, Qian,Zhang, Zheng,Zhao, Lei,Qin, Yun,Cai, Haodong...&Zhou, Jianfeng.(2020).Tropism-facilitated delivery of CRISPR/Cas9 system with chimeric antigen receptor-extracellular vesicles against B-cell malignancies.JOURNAL OF CONTROLLED RELEASE,326,
MLA:
Xu, Qian,et al."Tropism-facilitated delivery of CRISPR/Cas9 system with chimeric antigen receptor-extracellular vesicles against B-cell malignancies".JOURNAL OF CONTROLLED RELEASE 326.(2020):455-467