Generation of genetically tailored porcine liver cancer cells by CRISPR/Cas9 editing
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 TP53R167H 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2021
- Source ID
- 10.2144/btn-2020-0119
Entities
People
- Kelly Garcia
- Kimia Dasteh Goli
- Kyle M. Schachtschneider
- Lawrence B. Schook
- Lobna Elkhadragy
- Matthew Stewart
- Maureen R Regan
- Ron C Gaba
- Shovik Patel
- William M Totura
Organizations
- National Cancer Institute
- United States Department of Defense
- University of Illinois Urbana–Champaign
- University of Illinois at Chicago