Abstract
BackgroundThe 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.ResultsHere 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.ConclusionsCRISPR/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.
Highlights
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
Elimination of the Y chromosome in vitro and in vivo We initially examined whether complete elimination of a chromosome could be achieved efficiently by using CRISPR/Cas9-mediated multiple cuts at chromosomespecific sites
We examined whether the mouse Y chromosome contains unique repeated sequences that could be used for large-scale chromosomal editing via short-guide RNAs, and whether such editing could result in Y chromosome deletion
Summary
The CRISPR/Cas system has become an efficient gene editing method for generating cells carrying precise gene mutations, including the rearrangement and deletion of chromosomal segments. CRISPR/Cas9mediated genome editing has been applied to generate cells or animals carrying precise gene mutations [5, 6], Zuo et al Genome Biology (2017) 18:224 including rearrangements [7, 8] and deletion of chromosome segments [9]. We 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
