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유전체 항상성 연구단
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Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9

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Title
Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9
Author(s)
Taejoon Kwon; Jae Sun Ra; Lee, Soyoung; In-Joon Baek; Khim, Keon Woo; Eun A. Lee; Song, Eun Kyung; Daniyar Otarbayev; Woojae Jung; Yong Hwan Park; Minwoo Wie; Bae, Juyoung; Cheng, Himchan; Jun Hong Park; Namwoo Kim; Yuri Seo; Yun, Seongmin; Kim, Ha Eun; Moon, Hyo Eun; Paek, Sun Ha; Tae Joo Park; Park, Young Un; Rhee, Hwanseok; Jang Hyun Choi; Seung Woo Cho; Kyungjae Myung
Publication Date
2022-02
Journal
Proceedings of the National Academy of Sciences of the United States of America, v.119, no.9
Publisher
National Academy of Sciences
Abstract
© 2022 National Academy of Sciences. All rights reserved.An ideal cancer therapeutic strategy involves the selective killing of cancer cells without affecting the surrounding normal cells. However, researchers have failed to develop such methods for achieving selective cancer cell death because of shared features between cancerous and normal cells. In this study, we have developed a therapeutic strategy called the cancer-specific insertions–deletions (InDels) attacker (CINDELA) to selectively induce cancer cell death using the CRISPR-Cas system. CINDELA utilizes a previously unexplored idea of introducing CRISPR-mediated DNA double-strand breaks (DSBs) in a cancer-specific fashion to facilitate specific cell death. In particular, CINDELA targets multiple InDels with CRISPRCas9 to produce many DNA DSBs that result in cancer-specific cell death. As a proof of concept, we demonstrate here that CINDELA selectively kills human cancer cell lines, xenograft human tumors in mice, patient-derived glioblastoma, and lung patient-driven xenograft tumors without affecting healthy human cells or altering mouse growth.
URI
https://pr.ibs.re.kr/handle/8788114/12955
DOI
10.1073/pnas.2103532119
ISSN
0027-8424
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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