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CRISPR/Cas9-mediated targeted chromosome elimination

Author:
Zuo, Erwei, Huo, Xiaona, Yao, Xuan, Hu, Xinde, Sun, Yidi, Yin, Jianhang, He, Bingbing, Wang, Xing, Shi, Linyu, Ping, Jie, Wei, Yu, Ying, Wenqin, Wei, Wei, Liu, Wenjia, Tang, Cheng, Li, Yixue, Hu, Jiazhi, Yang, Hui
Source:
Genome biology 2017 v.18 no.1 pp. 224
ISSN:
1474-760X
Subject:
RNA, animal models, chromosome elimination, cultured cells, embryonic stem cells, gene editing, genes, humans, induced pluripotent stem cells, mice, mutation, neoplasm cells, neoplasms, sex chromosomes, trisomics
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.
Agid:
5866803