title: Targeting ABCB1-mediated tumor multidrug resistance by CRISPR/Cas9-based genome editing.
abstract: The RNA-guided clustered regularly interspaced short palindromic (CRISPR) in combination with a CRISPR-associated nuclease 9 (Cas9) nuclease system is a new rapid and precise technology for genome editing. In the present study, we applied the CRISPR/Cas9 system to target ABCB1 (also named MDR1) gene which encodes a 170 kDa transmembrane glycoprotein (P-glycoprotein/P-gp) transporting multiple types of chemotherapeutic drugs including taxanes, epipodophyllotoxins, vinca alkaloids and anthracyclines out of cells to contribute multidrug resistance (MDR) in cancer cells. Our data showed that knockout of ABCB1 by CRISPR/Cas9 system was succesfully archieved with two target sgRNAs in two MDR cancer cells due to the alteration of genome sequences. Knockout of ABCB1 by CRISPR/Cas9 system significantly enhances the sensitivity of ABCB1 substrate chemotherapeutic agents and the intracellular accumulation of rhodamine 123 and doxorubicin in MDR cancer cells. Although now there are lots of limitations to the application of CRISPR/Cas9 for editing cancer genes in human patients, our study provides valuable clues for the use of the CRISPR/Cas9 technology in the investigation and conquest of cancer MDR.
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Jian-Ge
authors.initials: JG
authors.lastname: Qiu
authors.affiliation: Department of Gastrointertinal Surgery & General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080, Guangdong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, The 3rd Affiliated Hospital of Sun Yat-sen University Guangzhou 510630, Guangdong, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Di
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Wen-Ji
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Di-Wei
authors.initials: DW
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Meng-Ning
authors.initials: MN
authors.lastname: Wei
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Huang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine Guangzhou 510632, Guangdong, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
keywords: ABCB1; CRISPR/Cas9; multidrug resistance; tumor