Chow Ryan D, Chen Sidi
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; Systems Biology Institute, Yale University School of Medicine, West Haven, CT, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA.
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA; Systems Biology Institute, Yale University School of Medicine, West Haven, CT, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA; Biological and Biomedical Sciences Program, Yale University School of Medicine, New Haven, CT, USA; Immunobiology Program, Yale University School of Medicine, New Haven, CT, USA; Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA; Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.
Trends Cancer. 2018 May;4(5):349-358. doi: 10.1016/j.trecan.2018.03.002. Epub 2018 Mar 30.
Clustered regularly interspaced short palindromic repeats (CRISPR) screening is a powerful toolset for investigating diverse biological processes. Most CRISPR screens to date have been performed with in vitro cultures or cellular transplant models. To interrogate cancer in animal models that more closely recapitulate the human disease, autochthonous direct in vivo CRISPR screens have recently been developed that can identify causative drivers in the native tissue microenvironment. By empowering multiplexed mutagenesis in fully immunocompetent animals, direct in vivo CRISPR screens enable the rapid generation of patient-specific avatars that can guide precision medicine. This Opinion article discusses the current status of in vivo CRISPR screens in cancer and offers perspectives on future applications.
成簇规律间隔短回文重复序列(CRISPR)筛选是用于研究多种生物学过程的强大工具集。迄今为止,大多数CRISPR筛选都是在体外培养物或细胞移植模型中进行的。为了在更能重现人类疾病的动物模型中研究癌症,最近开发了原位直接体内CRISPR筛选,其可以在天然组织微环境中识别致病驱动因素。通过在完全具有免疫活性的动物中实现多重诱变,直接体内CRISPR筛选能够快速生成可指导精准医学的患者特异性模型。这篇观点文章讨论了癌症体内CRISPR筛选的现状,并对未来应用提出了看法。