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CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression

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Title
CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression
Author(s)
Yoon, A.-R.; Jung, B.-K.; Choi, E.; Chung, E.; Hong, J.; Jin-Soo Kim; Koo, T.; Yun, C.-O.
Publication Date
2020-10
Journal
MOLECULAR THERAPY, v.28, no.10, pp.2286 - 2296
Publisher
CELL PRESS
Abstract
© 2020 The American Society of Gene and Cell Therapy. 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. Oncolytic adenovirus expressing CRISPR-Cas12a, which combines the strong oncolytic effect of oAd with precise and cancer-specific CRISPR-mediated oncogene disruption, potentiates antitumor effects
URI
https://pr.ibs.re.kr/handle/8788114/7619
DOI
10.1016/j.ymthe.2020.07.003
ISSN
1525-0016
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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