Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression
- Title
- Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression
- Author
- 윤채옥
- Keywords
- CELL LUNG-CANCER; IN-VIVO; EGFR MUTATIONS; PROSTATE-CANCER; GENE KNOCKOUT; GROWTH; CRISPR-CAS9; DISEASE; ADENOVIRUSES; RESISTANCE
- Issue Date
- 2017-07
- Publisher
- OXFORD UNIV PRESS
- Citation
- NUCLEIC ACIDS RESEARCH, v. 45, no. 13, page. 7897-7908
- 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.
- URI
- https://academic.oup.com/nar/article/45/13/7897/3859019https://repository.hanyang.ac.kr/handle/20.500.11754/114758
- ISSN
- 0305-1048; 1362-4962
- DOI
- 10.1093/nar/gkx490
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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