Rapid interrogation of cancer cell of origin through CRISPR editing Journal Article


Authors: Feng, W.; Cao, Z.; Lim, P. X.; Zhao, H.; Luo, H.; Mao, N.; Lee, Y. S.; Agudelo Rivera, A.; Choi, D.; Wu, C.; Han, T.; Romero, R.; de Stanchina, E.; Carver, B. S.; Wang, Q.; Jasin, M.; Sawyers, C. L.
Article Title: Rapid interrogation of cancer cell of origin through CRISPR editing
Abstract: The increasing complexity of different cell types revealed by single-cell analysis of tissues presents challenges in efficiently elucidating their functions. Here we show, using prostate as a model tissue, that primary organoids and freshly isolated epithelial cells can be CRISPR edited ex vivo using Cas9-CsgRNA (guide RNA) ribotnucleoprotein complex technology, then orthotopically transferred in vivo into immunocompetent or immunodeficient mice to generate cancer models with phenotypes resembling those seen in traditional genetically engineered mouse models. Large intrachromosomal (∼2 Mb) or multigenic deletions can be engineered efficiently without the need for selection, including in isolated subpopulations to address cell-of-origin questions. © 2021 National Academy of Sciences. All rights reserved.
Keywords: cancer modeling; editing; crispr; organoids
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 118
Issue: 32
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2021-08-10
Start Page: e2110344118
Language: English
DOI: 10.1073/pnas.2110344118
PROVIDER: scopus
PMCID: PMC8364185
PUBMED: 34353917
DOI/URL:
Notes: Article -- Export Date: 1 September 2021 -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    219 Sawyers
  2. Maria Jasin
    246 Jasin
  3. Brett Stewart Carver
    137 Carver
  4. Weiran Feng
    7 Feng
  5. Zhen Cao
    22 Cao
  6. Ninghui   Mao
    18 Mao
  7. HuiYong   Zhao
    24 Zhao
  8. Pei Xin   Lim
    5 Lim
  9. Chao Wu
    18 Wu
  10. Danielle Wai-pui Li
    12 Li
  11. Young Sun Lee
    10 Lee
  12. Hanzhi Luo
    20 Luo
  13. Teng Han
    3 Han
  14. Rodrigo Romero
    1 Romero