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Chromosome Could Be Eliminated by CRISPR/Cas9-mediated Genome Editing

Nov 27, 2017     Email"> PrintText Size

Type II bacterial CRISPR/Cas9 system has been engineered into an efficient genome editing tool consisting of the Cas9 nuclease and a single guide RNA (sgRNA), dramatically transforming the ability to edit the genomes of diverse organisms. The sgRNA targets Cas9 to genomic regions to induce double-stranded DNA breaks, which are repaired by nonhomologous end-joining or homology-directed repair.

In a recent study published in Genome Biology, Dr. YANG Hui’s Lab at the Institute of Neuroscience, the Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences (CAS), and Dr. HU Jiazhi’s Lab at the Peking University demonstrated that an entire Chromosome could be eliminated by CRISPR/Cas9-mediated genome editing.

CRISPR/Cas9–mediate genome editing has been applied to generate cells or animals carrying precise gene mutations, rearrangement and deletion of chromosome segments. The researchers asked whether this powerful technology could be used for targeted chromosome elimination to generate animal models with chromosome deletion in various species and to treat human aneuploidy diseases involving chromosome addition.

This study utilized a new application of the CRISPR/Cas9 technology by which a single specific chromosome could be selectively eliminated via multiple DNA cleavages on the targeted chromosome in culture cells, embryos and in vivo tissues. CRISPR/Cas9-mediated targeted chromosome elimination offers a new approach in developing animal models and therapeutic treatments for aneuploidy.

To test this idea, they first demonstrated that Y chromosome could be efficiently eliminated in mouse embryonic stem (ES) cells using CRISPR/Cas9-mediated multiple DNA cleavages at Y chromosome. These cleavages were induced by a single sgRNA or two sgRNAs that targeted multiple chromosome-specific sites, or by a cocktail of 14 sgRNAs, with each targeting one specific site.

In addition, they showed that mouse X chromosome, human chromosome seven and 14 could be selectively eliminated in cultured cells or embryos. Human chromosome 21 in human induced pluripotent stem cells (iPSCs) with trisomy 21 was also eliminated.

This was the first report on X and autosome chromosome elimination via genome editing, which paves the way for studying aneuploidy in tumorigenesis and chromosome therapy in vivo.

This work was supported by National Science and Technology Major Project, CAS Strategic Priority Research Program, the MoST863 Program, NSFC grants, China Youth Thousand Talents Program, Break through project of Chinese Academy of Sciences.

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(Editor: LIU Jia)

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