One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids

This study focuses on the application of CRISPR/Cas9-mediated base editors for creating complex tumor models using human ASC-derived organoids. They first demonstrated the effectiveness of base editors in introducing specific mutations associated with CTNNB1 in hepatocyte organoids. Base editors  were then used to insert nonsense mutations in PTEN in endometrial organoids, leading to tumorigenicity, even in the heterozygous state. Drug sensitivity assays on these organoids provided insights into early stages of endometrial tumorigenesis. The researchers combined different Cas9 enzymes to enable simultaneous editing of multiple target sites, expanding the scope of base editing. Lastly, they used base editor multiplexing to model colorectal tumorigenesis efficiently by targeting multiple cancer-related genes in a single step.

Keywords: Organoid