Application of CRISPR for In Vivo Mouse Cancer Studies

SIMPLE SUMMARY: Clustered regularly interspaced short palindromic repeats (CRISPR) were discovered in prokaryotes, and the technology can also be used to edit the genome in mammalian cells. The discovery was awarded the Nobel Prize in 2020, as CRISPR has opened up new possibilities to edit the human genome. CRISPR has been applied to study cancer because the method allows for many new ways to model the disease. This includes the development of pre-clinical models of cancer, where CRISPR is used to generate mutations that are found in human cancer. Therefore, unique mutations can be studied in a physiologically relevant setting, and CRISPR technology has accelerated the engineering of these models. This review focuses on exploring the current knowledge of CRISPR editing in adult tissues for generating pre-clinical models to study cancer. ABSTRACT: Clustered regularly interspaced short palindromic repeats (CRISPR) are widely used in cancer research to edit specific genes and study their functions. This applies both to in vitro and in vivo studies where CRISPR technology has accelerated the generation of specific loss- or gain-of-function mutations. This review focuses on CRISPR for generating in vivo models of cancer by editing somatic cells in specific organs. The delivery of CRISPR/Cas to designated tissues and specific cell compartments is discussed with a focus on different methods and their advantages. One advantage of CRISPR/Cas is the possibility to target multiple genes simultaneously in the same cell and therefore generate complex mutation profiles. This complexity challenges the interpretation of results and different methods to analyze the samples discussed herein. CRISPR-induced tumors are also different from classical tumors in pre-clinical models. Especially the clonal evolution of CRISPR-induced tumors adds new insight into cancer biology. Finally, the review discusses future perspectives for CRISPR technology in pre-clinical models with a focus on in vivo screening, CRISPR activation/inhibition, and the development of prime/ base-editing for the introduction of specific gene editing.