Ha, Jong Seong Byun, Juyoung Ahn, Dae-Ro 2024-01-20T04:33:50Z 2024-01-20T04:33:50Z 2021-09-05 2016-03-10 2045-2322 https://pubs.kist.re.kr/handle/201004/124288 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. English NATURE PUBLISHING GROUP SMALL INTERFERING RNA MULTIDRUG-RESISTANCE DRUG-RESISTANCE P-GLYCOPROTEIN TUMOR-CELLS DELIVERY CRISPR-CAS9 CRISPR/CAS9 STRATEGIES IMMUNITY Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption Article 10.1038/srep22847 1 SCIENTIFIC REPORTS, v.6 SCIENTIFIC REPORTS 6 scie scopus 000371728400003 2-s2.0-84960891137 Multidisciplinary Sciences Science & Technology - Other Topics Article SMALL INTERFERING RNA MULTIDRUG-RESISTANCE DRUG-RESISTANCE P-GLYCOPROTEIN TUMOR-CELLS DELIVERY CRISPR-CAS9 CRISPR/CAS9 STRATEGIES IMMUNITY Cas9 CRISPR Drug resistance cancer doxorubicin