Rapid interrogation of cancer cell of origin through CRISPR editing.

Publication Type	Academic Article
Authors	Feng W, Cao Z, Lim P, Zhao H, Luo H, Mao N, Lee Y, Rivera A, Choi D, Wu C, Han T, Romero R, de Stanchina E, Carver B, Wang Q, Jasin M, Sawyers C
Journal	Proc Natl Acad Sci U S A
Volume	118
Issue	32
Date Published	08/10/2021
ISSN	1091-6490
Keywords	Chromosome Deletion, Clustered Regularly Interspaced Short Palindromic Repeats, Gene Editing, Prostate
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.
DOI	10.1073/pnas.2110344118
PubMed ID	34353917
PubMed Central ID	PMC8364185