Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.
Oncode Institute and Division of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, Netherlands.
Curr Opin Genet Dev. 2021 Feb;66:57-62. doi: 10.1016/j.gde.2020.12.005. Epub 2021 Jan 8.
CRISPR/Cas9 systems have revolutionised the field of gene editing, allowing for precise modifications to be generated in vivo to mimic the genetic events found in human cancer cells. These systems may be used to generate germline or somatic loss-of-function of events, and also chromosomal rearrangements, either constitutively or in a spatiotemporally controlled manner. Forward genetic screens have also been performed using CRISPR/Cas9 systems to identify new driver genes and approaches using catalytically inactive Cas9 fused to base editors have enabled genome editing with single-base precision. Here we discuss the many 'flavours' of the CRISPR/Cas9 system and give examples of their use for the generation of clinically-relevant mouse models of cancer.
CRISPR/Cas9 系统彻底改变了基因编辑领域，使得能够在体内产生精确的修饰，以模拟人类癌细胞中的遗传事件。这些系统可用于产生种系或体细胞功能丧失事件，以及染色体重排，无论是组成型还是时空控制方式。还使用 CRISPR/Cas9 系统进行了正向遗传筛选，以鉴定新的驱动基因，并且使用与碱基编辑器融合的无催化活性 Cas9 的方法使得具有单碱基精度的基因组编辑成为可能。在这里，我们讨论了 CRISPR/Cas9 系统的许多“变体”，并举例说明了它们在生成临床相关的癌症小鼠模型中的应用。
