title: Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption.
abstract: In this study, Cas9 system was employed to down-regulate mdr1 gene for overcoming multidrug resistance of cancer cells. Disruption of the MDR1 gene was achieved by delivery of the Cas9-sgRNA plasmid or the Cas9-sgRNA ribonucleoprotein complex using a conventional gene transfection agent and protein transduction domain (PTD). Doxorubicin showed considerable cytotoxicity to the drug-resistant breast cancer cells pre-treated with the RNA-guided endonuclease (RGEN) systems, whereas virtually non-toxic to the untreated cells. The potency of drug was enhanced in the cells treated with the protein-RNA complex as well as in those treated with plasmids, suggesting that mutation of the mdr1 gene by intracellular delivery of Cas9-sgRNA complex using proper protein delivery platforms could recover the drug susceptibility. Therefore, Cas9-mediated disruption of the drug resistance-related gene can be considered as a promising way to overcome multidrug resistance in cancer cells.
authors.affiliation: The Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Ha
authors.affiliation: Department of Biological Chemistry, KIST School, University of Science and Technology (UST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Juyoung
authors.initials: J
authors.lastname: Byun
authors.affiliation: The Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.|Department of Biological Chemistry, KIST School, University of Science and Technology (UST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Dae-Ro
authors.initials: DR
authors.lastname: Ahn
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D014162:Transfection; D000094704:RNA, Guide, CRISPR-Cas Systems
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D000094704:RNA, Guide, CRISPR-Cas Systems