Thomsen Martin K
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
Aarhus Institute of Advanced Studies (AIAS), Aarhus University, 8000 Aarhus, Denmark.
Cancers (Basel). 2022 Oct 13;14(20):5014. doi: 10.3390/cancers14205014.
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.
成簇规律间隔短回文重复序列(CRISPR)在癌症研究中被广泛用于编辑特定基因并研究其功能。这适用于体外和体内研究,在这些研究中,CRISPR技术加速了特定功能丧失或功能获得突变的产生。本综述重点关注通过编辑特定器官中的体细胞来生成癌症体内模型的CRISPR。讨论了将CRISPR/Cas递送至指定组织和特定细胞区室的方法,重点是不同方法及其优势。CRISPR/Cas的一个优点是有可能在同一细胞中同时靶向多个基因,从而生成复杂的突变谱。这种复杂性对结果的解释以及本文讨论的分析样本的不同方法提出了挑战。CRISPR诱导的肿瘤在临床前模型中也与经典肿瘤不同。特别是CRISPR诱导肿瘤的克隆进化为癌症生物学提供了新的见解。最后,本综述讨论了CRISPR技术在临床前模型中的未来前景,重点是体内筛选、CRISPR激活/抑制以及用于引入特定基因编辑的引导编辑/碱基编辑的发展。