1. Generation of genetically tailored porcine liver cancer cells by CRISPR/Cas9 editing.
- Author
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Elkhadragy L, Regan MR, M Totura W, Goli KD, Patel S, Garcia K, Stewart M, Schook LB, Gaba RC, and Schachtschneider KM
- Subjects
- Animals, Cell Line, Gene Editing, Swine, CRISPR-Cas Systems, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics
- Abstract
Pigs provide a valuable large animal model for several diseases due to their similarity with humans in anatomy, physiology, genetics and drug metabolism. We recently generated a porcine model for TP53
R167H and KRASG12D driven hepatocellular carcinoma (HCC) by autologous liver implantation. Here we describe a streamlined approach for developing genetically tailored porcine HCC cells by CRISPR/Cas9 gene editing and isolation of homogenous genetically validated cell clones. The combination of CRISPR/Cas9 editing of HCC cells described herein with the orthotopic HCC model enables development of various porcine HCC models, each with a specific mutational profile. This allows modeling the effect of different driver mutation combinations on tumor progression and in vivo testing of novel targeted therapeutic approaches in a clinically relevant large animal model.- Published
- 2021
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