Cited by 276CRISPR and Genetic EngineeringRNA regulation and diseaseAnimal Genetics and Reproduction

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

Zhou, Haibo, Liu, Junlai, Zhou, Changyang, Gao, Ni, Rao, Zhiping, Li, He, Hu, Xinde, Li, Changlin, Yao, Xuan, Shen, Xiaowen, Sun, Yidi, Wei, Yu, Liu, Fei, Ying, Wenqin, Zhang, Junming, Tang, Cheng, Zhang, Xu, Xu, Huatai, Shi, Linyu, Cheng, Leping, Huang, Pengyu, Yang, Hui·2018·Nature Neuroscience

DOI 10.1038/s41593-017-0060-6

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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.

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Authors: 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.
Affiliations: Chinese Academy of Sciences (CN)
ShanghaiTech University (CN)
Corresponding author: Huang, Pengyu
Yang, Hui
ORCID: Zhou, Haibo
Zhou, Changyang
Li, He
Hu, Xinde
Li, Changlin
Yao, Xuan
Sun, Yidi
Liu, Fei
Ying, Wenqin
Zhang, Junming
Tang, Cheng
Zhang, Xu
Xu, Huatai
Shi, Linyu
Huang, Pengyu
Yang, Hui
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2018-01-15
Volume: 21
Issue: 3
Pages: 440-446
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/s41593-017-0060-6
OpenAlex: W2783322400
Cited by: 276
References: 57
Citations by year: 2026: 10 · 2025: 26 · 2024: 37 · 2023: 36 · 2022: 38 · 2021: 35 · 2020: 39 · 2019: 34 · 2018: 20
FWCI: 11.38
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords: CRISPR/dCas9, transcriptional activation, transgenic mice, long non-coding RNA, astrocyte-to-neuron conversion, neurogenesis, gene networks, brain
MeSH terms: Animals, Astrocytes, Brain Chemistry, DNA-Binding Proteins, Female, Male, Mice, Transgenic, Nerve Tissue Proteins, Nervous System, Neurons, Nuclear Proteins, Transcriptional Activation, Mice, Primary Cell Culture, RNA, Long Noncoding, CRISPR-Cas Systems

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

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