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유전체교정연구단
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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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dc.contributor.authorYoon, A.-R.-
dc.contributor.authorJung, B.-K.-
dc.contributor.authorChoi, E.-
dc.contributor.authorChung, E.-
dc.contributor.authorHong, J.-
dc.contributor.authorJin-Soo Kim-
dc.contributor.authorKoo, T.-
dc.contributor.authorYun, C.-O.-
dc.date.accessioned2020-12-22T02:44:34Z-
dc.date.accessioned2020-12-22T02:44:34Z-
dc.date.available2020-12-22T02:44:34Z-
dc.date.available2020-12-22T02:44:34Z-
dc.date.created2020-09-09-
dc.date.issued2020-10-
dc.identifier.issn1525-0016-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/7619-
dc.description.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-
dc.description.uri1-
dc.language영어-
dc.publisherCELL PRESS-
dc.titleCRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000579536500018-
dc.identifier.scopusid2-s2.0-85088115715-
dc.identifier.rimsid72766-
dc.contributor.affiliatedAuthorJin-Soo Kim-
dc.identifier.doi10.1016/j.ymthe.2020.07.003-
dc.identifier.bibliographicCitationMOLECULAR THERAPY, v.28, no.10, pp.2286 - 2296-
dc.citation.titleMOLECULAR THERAPY-
dc.citation.volume28-
dc.citation.number10-
dc.citation.startPage2286-
dc.citation.endPage2296-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.subject.keywordPlusONCOLYTIC ADENOVIRUS-
dc.subject.keywordPlusACQUIRED-RESISTANCE-
dc.subject.keywordPlusCRISPR-CAS-
dc.subject.keywordPlusDL1520 ONYX-015-
dc.subject.keywordPlusGENE DELIVERY-
dc.subject.keywordPlusLUNG-CANCER-
dc.subject.keywordPlusPHASE-II-
dc.subject.keywordPlusCPF1-
dc.subject.keywordPlusMET-
dc.subject.keywordPlusANGIOGENESIS-
dc.subject.keywordAuthoranti-tumor effect-
dc.subject.keywordAuthorCas12a-
dc.subject.keywordAuthorCpf1-
dc.subject.keywordAuthorCRISPR-
dc.subject.keywordAuthorEGFR-
dc.subject.keywordAuthorgenome editing-
dc.subject.keywordAuthoroncolytic virus-
dc.subject.keywordAuthorout-of-frame-
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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