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Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression
DC Field | Value | Language |
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dc.contributor.author | Koo, Taeyoung | - |
dc.contributor.author | Yoon, A-Rum | - |
dc.contributor.author | Cho, Hee-Yeon | - |
dc.contributor.author | Bae, Sangsu | - |
dc.contributor.author | Yun, Chae-Ok | - |
dc.contributor.author | Kim, Jin-Soo | - |
dc.date.accessioned | 2020-04-27T12:52:07Z | - |
dc.date.available | 2020-04-27T12:52:07Z | - |
dc.date.created | 2018-09-04 | - |
dc.date.created | 2018-09-04 | - |
dc.date.issued | 2017-07 | - |
dc.identifier.citation | Nucleic Acids Research, Vol.45 No.13, pp.7897-7908 | - |
dc.identifier.issn | 0305-1048 | - |
dc.identifier.other | 49949 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165680 | - |
dc.description.abstract | Approximately 15% of non-small cell lung cancer cases are associated with a mutation in the epidermal growth factor receptor (EGFR) gene, which plays a critical role in tumor progression. With the goal of treating mutated EGFR-mediated lung cancer, we demonstrate the use of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system to discriminate between the oncogenic mutant and wild-type EGFR alleles and eliminate the carcinogenic mutant EGFR allele with high accuracy. We targeted an EGFR oncogene harboring a single-nucleotide missense mutation (CTG > CGG) that generates a protospacer-adjacent motif sequence recognized by the CRISPR/Cas9 derived from Streptococcus pyogenes. Co-delivery of Cas9 and an EGFR mutation-specific single-guide RNA via adenovirus resulted in precise disruption at the oncogenic mutation site with high specificity. Furthermore, this CRISPR/Cas9-mediated mutant allele disruption led to significantly enhanced cancer cell killing and reduced tumor size in a xenograft mouse model of human lung cancer. Taken together, these results indicate that targeting an oncogenic mutation using CRISPR/Cas9 offers a powerful surgical strategy to disrupt oncogenic mutations to treat cancers; similar strategies could be used to treat other mutation-associated diseases. | - |
dc.language | 영어 | - |
dc.publisher | Oxford University Press | - |
dc.title | Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김진수 | - |
dc.identifier.doi | 10.1093/nar/gkx490 | - |
dc.citation.journaltitle | Nucleic Acids Research | - |
dc.identifier.wosid | 000406776400039 | - |
dc.identifier.scopusid | 2-s2.0-85026466724 | - |
dc.citation.endpage | 7908 | - |
dc.citation.number | 13 | - |
dc.citation.startpage | 7897 | - |
dc.citation.volume | 45 | - |
dc.identifier.sci | 000406776400039 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Jin-Soo | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | EGFR MUTATIONS | - |
dc.subject.keywordPlus | PROSTATE-CANCER | - |
dc.subject.keywordPlus | GENE KNOCKOUT | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | CRISPR-CAS9 | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | ADENOVIRUSES | - |
dc.subject.keywordPlus | RESISTANCE | - |
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