Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression

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Title
Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression
Author(s)
Taeyoung Koo; A-Rum Yoon; Hee-Yeon Cho; Sangsu Bae; Chae-Ok Yun; Jin-Soo Kim
Publication Date
2017-07
Journal
NUCLEIC ACIDS RESEARCH, v.45, no.13, pp.7897 - 7908
Publisher
OXFORD UNIV PRESS
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 treatingmutatedEGFR-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 mutationassociated diseases. © The Author(s) 2017
URI
https://pr.ibs.re.kr/handle/8788114/3653
ISSN
0305-1048
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
Files in This Item:
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