CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression
- Title
- CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression
- Author
- 윤채옥
- Keywords
- ONCOLYTIC ADENOVIRUS; ACQUIRED-RESISTANCE; CRISPR-CAS; DL1520 ONYX-015; GENE DELIVERY; LUNG-CANCER; PHASE-II; CPF1; MET; ANGIOGENESIS
- Issue Date
- 2020-10
- Publisher
- CELL PRESS
- Citation
- MOLECULAR THERAPY, v. 28, NO 10, Page. 2286-2296
- Abstract
- CRISPR-Cas12a represents a class 2/type V CRISPR RNA-guided endonuclease, holding promise as a precise genome-editing tool in vitro and in vivo. For efficient delivery of the CRISPR-Cas system into cancer, oncolytic adenovirus (oAd) has been recognized as a promising alternative vehicle to conventional cancer therapy, owing to its cancer specificity; however, to our knowledge, it has not been used for genome editing. In this study, we show that CRISPR-Cas12a mediated by oAd disrupts the oncogenic signaling pathway with excellent cancer specificity. The intratumoral delivery of a single oAd co-expressing a Cas12a and a CRISPR RNA (crRNA) targeting the epidermal growth factor receptor (EGFR) gene (oAd/Cas12a/crEGFR) induces efficient and precise editing of the targeted EGFR gene in a cancer-specific manner, without detectable off-target nuclease activity. Importantly, oAd/Cas12a/crEGFR elicits a potent antitumor effect via robust induction of apoptosis and inhibition of tumor cell proliferation, ultimately leading to complete tumor regression in a subset of treated mice. Collectively, in this study we show precise genomic reprogramming via a single oAd vector-mediated CRISPR-Cas system and the feasibility of such system as an alternative cancer therapy.
- URI
- https://www.sciencedirect.com/science/article/pii/S1525001620303543?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/171935
- ISSN
- 1525-0016; 1525-0024
- DOI
- 10.1016/j.ymthe.2020.07.003
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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