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Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9.
Kwon, Taejoon; Ra, Jae Sun; Lee, Soyoung; Baek, In-Joon; Khim, Keon Woo; Lee, Eun A; Song, Eun Kyung; Otarbayev, Daniyar; Jung, Woojae; Park, Yong Hwan; Wie, Minwoo; Bae, Juyoung; Cheng, Himchan; Park, Jun Hong; Kim, Namwoo; Seo, Yuri; Yun, Seongmin; Kim, Ha Eun; Moon, Hyo Eun; Paek, Sun Ha; Park, Tae Joo; Park, Young Un; Rhee, Hwanseok; Choi, Jang Hyun; Cho, Seung Woo; Myung, Kyungjae.
Affiliation
  • Kwon T; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea; tkwon@unist.ac.kr swcho@unist.ac.kr kmyung@ibs.re.kr.
  • Ra JS; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Lee S; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Baek IJ; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Khim KW; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Lee EA; Cascure Therapeutics, Ulsan 44919, Republic of Korea.
  • Song EK; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Otarbayev D; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Jung W; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Park YH; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Wie M; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Bae J; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Cheng H; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Park JH; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Kim N; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Seo Y; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Yun S; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Kim HE; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Moon HE; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Paek SH; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Park TJ; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Park YU; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
  • Rhee H; Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Choi JH; Department of Biological Sciences, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
  • Cho SW; Department of Neurosurgery, Seoul National University Hospital, Seoul 03080, Republic of Korea.
  • Myung K; Department of Neurosurgery, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Article in En | MEDLINE | ID: mdl-35217600
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 CRISPR-Cas9 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: INDEL Mutation / CRISPR-Cas Systems / Neoplasms Limits: Animals / Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: INDEL Mutation / CRISPR-Cas Systems / Neoplasms Limits: Animals / Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2022 Document type: Article Country of publication: United States