1. Rapid interrogation of cancer cell of origin through CRISPR editing.
- Author
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Weiran Feng, Zhen Cao, Pei Xin Lim, Huiyong Zhao, Hanzhi Luo, Ninghui Mao, Young Sun Lee, Rivera, Aura Agudelo, Choi, Danielle, Chao Wu, Teng Han, Romero, Rodrigo, de Stanchina, Elisa, Carver, Brett S., Qiao Wang, Jasin, Maria, and Sawyers, Charles L.
- Subjects
CRISPRS ,CANCER cells ,LABORATORY mice ,TISSUE analysis ,EPITHELIAL cells - 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-sgRNA (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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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