报告题目：CRISPR application in animals and gene therapies

报告人：杨辉，中国科学院神经科学研究所研究员

主持人：李大力 研究员

报告时间：2018年9月27日 下午16:00—17:00

报告地点：生命科学学院534小会议室

 

报告人简介：杨辉，2007年毕业于上海交通大学，2012年于中国科学院生物化学与细胞研究所获得博士学位，2012-2014在美国Whitehead研究所从事博士后研究，2014-至今任中国科学院神经科学研究所研究员。优秀青年科学基金等获得者。杨辉在基因编辑与基因治疗、干细胞与生殖发育、模式动物建立等领域取得一系列重要研究成果。研究成果以第一作者或通讯作者形式主要发表在Cell、Nature、Nature Neuroscience、Developmental Cell等国际学术刊物上，论文他引3000余次。

 

报告内容：The CRISPR/Cas9 technology provides a promising tool for genetic engineering. It offers an efficient approach to develop genetically modified (GM) animal models and a potential strategy for targeted gene therapies. We previously applied the CRISPR/Cas9 system to generate knockout mice and knock-in mice, although with mosaicism and relatively low efficiency. Recently, we optimized CRISPR/Cas9 system and obtained fully functional knockout mice and monkey in F0, which could be directly used for phenotypical analysis. We also devised a homology-mediated end joining (HMEJ)-based strategy, yielding knock-in mice and monkeys, with an efficiency much higher than other knock-in strategies. More recently, we developed a targeting strategy, termed Tild-CRISPR (targeted integration with linearized dsDNA- CRISPR). Compared with existing targeting strategies, this method achieved much higher knock-in efficiency in mouse and human embryos, as well as mouse brain using in utero electroporation. For targeted gene therapies, we rescued Fah−/− liver failure mice by correcting Fah mutation using microhomology-mediated end joining (MMEJ) and HMEJ-based strategies. Furthermore, we demonstrate the use of the CRISPR/Cas9 system to eliminate targeted chromosomes via multiple DNA cleavages, offering a new therapeutic strategy for human aneuploidy diseases involving additional chromosomes. Finally, we achieved multiple genes activation in vivo using CRISPR–dCas9- activator, leading to observable phenotypic changes in liver and brain. This offers a new approach for developing targeted epigenetic therapies against human diseases.