CRISPR/Cas9-mediated targeted chromosome elimination. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Genome biology. Volume 18:Issue 1(2017)
• Page Start: 1
• Page End: 18
• Publication Date: 2017-12
• Subjects: Genomes -- Periodicals; Biology -- Periodicals; Molecular biology -- Periodicals; 572.8633
• DOI: 10.1186/s13059-017-1354-4
• Languages: English
• ISSNs: 1474-760X

Abstract

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.