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Genome Biol. 2017 Nov 24;18(1):224. doi: 10.1186/s13059-017-1354-4.

CRISPR/Cas9-mediated targeted chromosome elimination.

Zuo E1, Huo X1, Yao X1, Hu X1, Sun Y2, Yin J3, He B1,4, Wang X1,4, Shi L1, Ping J5, Wei Y1,6, Ying W1, Wei W1,7, Liu W1, Tang C1, Li Y2, Hu J8, Yang H9.

Author information

1
Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
2
Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
3
State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
4
University of Chinese Academy of Sciences, Shanghai, 200031, China.
5
Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA.
6
Shanghai University, Shanghai, 200444, China.
7
College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, 530004, China.
8
State Key Laboratory of Membrane Biology and Minstry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. hujz@pku.edu.cn.
9
Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. huiyang@ion.ac.cn.

Abstract

BACKGROUND:

The CRISPR/Cas9 system has become an efficient gene editing method for generating cells carrying precise gene mutations, including the rearrangement and deletion of chromosomal segments. However, whether an entire chromosome could be eliminated by this technology is still unknown.

RESULTS:

Here we demonstrate the use of the CRISPR/Cas9 system to eliminate targeted chromosomes. Using either multiple cleavages induced by a single-guide RNA (sgRNA) that targets multiple chromosome-specific sites or a cocktail of multiple sgRNAs, each targeting one specific site, we found that a sex chromosome could be selectively eliminated in cultured cells, embryos, and tissues in vivo. Furthermore, this approach was able to produce a targeted autosome loss in aneuploid mouse embryonic stem cells with an extra human chromosome and human induced pluripotent stem cells with trisomy 21, as well as cancer cells.

CONCLUSIONS:

CRISPR/Cas9-mediated targeted chromosome elimination offers a new approach to develop animal models with chromosome deletions, and a potential therapeutic strategy for human aneuploidy diseases involving additional chromosomes.

PMID:
29178945
PMCID:
PMC5701507
DOI:
10.1186/s13059-017-1354-4
[Indexed for MEDLINE]
Free PMC Article

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