[HTML][HTML] CRISPR/Cas9-mediated targeted chromosome elimination

E Zuo, X Huo, X Yao, X Hu, Y Sun, J Yin, B He, X Wang… - Genome biology, 2017 - Springer
E Zuo, X Huo, X Yao, X Hu, Y Sun, J Yin, B He, X Wang, L Shi, J Ping, Y Wei, W Ying, W Wei…
Genome biology, 2017Springer
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 …
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.
Springer