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Application of CRISPR for In Vivo Mouse Cancer Studies
1Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
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.
Insights
Clustered regularly interspaced short palindromic repeats (CRISPR) technology enables precise gene editing in vivo for cancer research. This review explores CRISPR applications in generating complex cancer models and analyzing their unique characteristics.
Area of Science:
- Genomics and Molecular Biology
- Cancer Research
- Biotechnology
Background:
- Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a powerful tool for gene editing in biological research.
- Its application in cancer research facilitates the study of gene function through loss- or gain-of-function mutations.
- CRISPR has significantly accelerated the creation of both in vitro and in vivo experimental models.
Purpose of the Study:
- To review the use of CRISPR for generating in vivo cancer models by editing somatic cells in specific organs.
- To discuss methods for delivering CRISPR/Cas systems to target tissues and cellular compartments.
- To explore the analysis of complex mutation profiles and the unique biology of CRISPR-induced tumors.
Main Methods:
- Focus on CRISPR/Cas delivery methods for in vivo gene editing in designated tissues.
- Discussion of simultaneous multi-gene targeting for complex mutation generation.
- Exploration of analytical techniques for complex genomic data and clonal evolution in CRISPR-induced tumors.
Main Results:
- CRISPR enables efficient generation of in vivo cancer models with specific mutations.
- Simultaneous targeting of multiple genes allows for the creation of complex genetic landscapes.
- CRISPR-induced tumors exhibit distinct characteristics, including clonal evolution, offering novel insights into cancer biology.
Conclusions:
- CRISPR technology is revolutionizing the creation and study of in vivo cancer models.
- Future perspectives include in vivo screening, CRISPR activation/inhibition, and advanced prime/base editing techniques.
- CRISPR holds significant promise for advancing preclinical cancer research and therapeutic development.
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