Journal Article

CRISPR/Cas9-mediated targeted chromosome elimination

Shi, Linyu, Huo, Xiaona, Hu, Xinde, Wei, Wei, Wang, Xing, Ying, Wenqin, Ping, Jie, Zuo, Erwei, Yang, Hui, Liu, Wenjia, Tang, Cheng, Yin, Jianhang, Li, Yixue, Yao, Xuan, Wei, Yu, He, Bingbing, Sun, Yidi, Hu, Jiazhi

2017

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aneuploidy / Animal Genetics and Genomics / Animal models / Animals / Bioinformatics / Biomedical and Life Sciences / Cancer / Chromosome Deletion / chromosome elimination / Chromosomes / Clonal deletion / Cloning / CRISPR / CRISPR-Cas Systems / cultured cells / Deoxyribonucleic acid / Disease Models, Animal / DNA / Embryo cells / Embryonic Stem Cells / Evolutionary Biology / Female / Gene deletion / Gene Editing / Gene rearrangement / Gene Targeting / Genes / Genetic engineering / Genome editing / Genomes / Genotype & phenotype / Human Genetics / humans / In Situ Hybridization, Fluorescence / induced pluripotent stem cells / Karyotype / Life Sciences / Male / Mice / Microbial Genetics and Genomics / Microinjections / Muscular dystrophy / mutation / neoplasm cells / neoplasms / Phenotype / Plant Genetics and Genomics / Plasmids / Pluripotency / Ribonucleic acid / RNA / RNA, Guide, CRISPR-Cas Systems / Science / sex chromosomes / Stem cell transplantation / Stem cells / trisomics / Trisomy / Turner Syndrome - genetics / Y Chromosome