演讲 · 嘉宾
杨辉

杨辉

中科院上海神经所

中科院上海神经所研究员,博士生导师,国家青年千人基金、优秀青年科学基金获得者。实验室致力于基因编辑技术的开发及其在疾病动物模型建立和疾病治疗中的应用。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, Cell Research, Genome Biology 等国际学术刊物上,论文他引3000余次。曾为Nature、Cell Research、Genome Biology等期刊审稿。

演讲报告题目摘要:

CRISPR application in animals and gene therapies
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. For targeted gene therapies, we have recently developed an off-target detection method named “GOTI” and found that cytosine base editor induced substantial off-target single nucleotide variants. Moreover, 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.

研究方向:

基因编辑及基因治疗

学习和工作经历:

教育经历(按时间倒排序):
2009/9 - 2012/7,中国科学院上海生命科学研究院,发育生物学,博士,导师:李劲松
2007/9 - 2009/7,中国科学院上海生命科学研究院,发育生物学,硕士,导师:李劲松
2003/9 - 2007/7,上海交通大学,生物技术,学士
工作经历(科研与学术工作经历,按时间倒序排序):
2014/5 - 至今,中国科学院上海生命科学研究院,神经科学研究所,研究员
2012/12 – 2014/05,美国麻省理工Whitehead研究所,博士后
2012/7 - 2012/12,中国科学院上海生命科学研究院,生物化学与细胞研究所,助理研究员

近期发表论文:

1. Yao, X., Liu, Z., Wang, X., Wang, Y., Nie, Y. H., Lai, L., Sun, R., Shi, L., Sun, Q.#, Yang, H.# (2017). Generation of Knock-in Cynomolgus Monkey via CRISPR/Cas9 Editing. Cell Research (In press)
2. Zhou, H., Liu, J., Zhou, C., Gao, N., Rao, Z., Li, H., Hu, X., Li, C., Yao, X., Shen, X., Sun, Y., Wei, Y., Liu, F., Ying, W., Zhang, J., Tang, C., Zhang, X., Xu, H., Shi, L., Cheng, L., Huang, P. #, Yang, H.# (2017). In vivo versatile transcriptional activation in the mammalian brain using CRISPR/dCas9-activator transgenic mice. Nature Neuroscience (In press)
3. Zuo, E.W., Huo, X.N., Yao, X., Hu, X.D., Sun, Y.D., Yin, J.H., He, B.B., Wang, X., Shi, L.Y., Ping, J., Wei, Y., Ying, W.Q., Wei, W., Liu, W.J., Tang, C., Li, Y.X., Hu, J.Z.# and Yang, H.# (2017) CRISPR/Cas9-mediated targeted chromosome elimination. Genome Biol. 18:224.
4. Zhou, C., Zhang, M., Wei, Y., Sun, Y., Sun, Y., Pan, H., Yao, N., Zhong, W., Li, Y., Li, W.#, Yang, H.#, Chen, Z.# (2017). Highly efficient base editing in human tripronuclear zygotes. Protein & Cell
5. Yao, X., Wang, X., Hu, X., Liu, Z., Liu, J., Zhou, H., Shen, X., Wei, Y., Huang, Z., Ying, W., Wang, Y., Nie, Y. H., Zhang, C. C., Li, S., Cheng, L., Wang, Q., Wu, Y., Huang, P., Sun, Q.#, Shi, L.#, Yang, H.# (2017). Homology-mediated end joining-based targeted integration using CRISPR/Cas9. Cell Research 27, 801-814.
6. Zuo, E., Cai, Y.J., Li, K., Wei, Y., Wang, B.A., Sun, Y., Liu, Z., Liu, J., Hu, X., Wei, W., Huo, X., Shi, L., Tang, C., Liang, D., Wang, Y., Nie, Y. H., Zhang, C. C., Yao, X., Wang, X., Zhou, C., Ying, W., Wang, Q., Chen, R. C., Shen, Q., Xu, G. L., Li, J. Sun, Q.#, Xiong, Z.#, Yang, H.# (2017). One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs. Cell Research 27:933-945
7. Yao, X., Wang, X., Liu, J., Hu, X., Shi, L., Shen, X., Ying, W., Sun, X., Wang, X., Huang, P.#, Yang, H.# (2017). CRISPR/Cas9 - Mediated Precise Targeted Integration In Vivo Using a Double Cut Donor with Short Homology Arms. EBioMedicine.
8. Yang, H.*, Wang, H.*, Shivalila, C.S.*, Cheng, A.W., Shi, L., and Jaenisch, R. (2013). One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering. Cell 154, 1370-1379.
9. Wang, H.*, Yang, H.*, Shivalila, C.S.*, Dawlaty, M.M., Cheng, A.W., Zhang, F., and Jaenisch, R. (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910-918.