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 |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work