清脆的
基因组编辑
体细胞
生物
计算生物学
克拉斯
癌变
Cas9
同源定向修复
基因
遗传学
突变
DNA修复
核苷酸切除修复
作者
Wen Bu,Chad J. Creighton,Kelsey S. Heavener,Carolina Gutiérrez,Yongchao Dou,Amy T. Ku,Yiqun Zhang,Weiyu Jiang,Jazmin Urrutia,Wen Jiang,Yue Fei,Luyu Jia,Ahmed Atef Ibrahim,Bing Zhang,Shixia Huang,Yi Li
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-05-12
卷期号:9 (19)
被引量:2
标识
DOI:10.1126/sciadv.ade0059
摘要
CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either Kras or Pik3ca in both normal and hyperplastic mammary glands led to swift tumorigenesis. The resulting tumors shared some histological, transcriptome, and proteome features with tumors induced by lentivirus-mediated expression of the respective oncogenes, but they also exhibited some distinct characteristics, particularly showing less intertumor variation, thus potentially offering more consistent models for cancer studies and therapeutic development. Therefore, this technological advance fills a critical gap between the power of CRISPR technology and high-fidelity mouse models for studying human tumor evolution and preclinical drug testing.
科研通智能强力驱动
Strongly Powered by AbleSci AI