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Nat Neurosci. 2018 Mar;21(3):440-446. doi: 10.1038/s41593-017-0060-6. Epub 2018 Jan 15.

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice.

Zhou H1, Liu J2,3,4, Zhou C1,3, Gao N1,3, Rao Z1,3, Li H1,3, Hu X1,3, Li C1, Yao X1, Shen X1, Sun Y5, Wei Y1, Liu F1,3, Ying W1, Zhang J1, Tang C1,3, Zhang X1, Xu H1, Shi L1, Cheng L1, Huang P6, Yang H7.

Author information

1
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
2
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
3
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
4
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
5
Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
6
School of Life Science and Technology, ShanghaiTech University, Shanghai, China. huangpy@shanghaitech.edu.cn.
7
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. huiyang@ion.ac.cn.

Abstract

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

PMID:
29335603
DOI:
10.1038/s41593-017-0060-6

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