Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep22847
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Funding
- Global Innovative Research Center program of the National Research Foundation of Korea [2012K1A1A2A01055811]
- Intramural Research Programs of KIST
- National Research Foundation of Korea (NRF) grant - Korea government (MSIP) [2014-R1A2A2A04002526]
- grant of the Korea Healthcare technology R&D Project, the Ministry of Health & Welfare, Republic of Korea [HI12C1093]
- Pioneer Research Center Program through NRF - Ministry of Science, ICT & Future Planning [2014M3C1A3054141]
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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.
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