Cargando…
CRISPR/Cas9-mediated targeted chromosome elimination
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. RESULT...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701507/ https://www.ncbi.nlm.nih.gov/pubmed/29178945 http://dx.doi.org/10.1186/s13059-017-1354-4 |
_version_ | 1783281357459292160 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Zuo, Erwei |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1354-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5701507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57015072017-12-04 CRISPR/Cas9-mediated targeted chromosome elimination 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 Genome Biol Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1354-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-24 /pmc/articles/PMC5701507/ /pubmed/29178945 http://dx.doi.org/10.1186/s13059-017-1354-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research 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 CRISPR/Cas9-mediated targeted chromosome elimination |
title | CRISPR/Cas9-mediated targeted chromosome elimination |
title_full | CRISPR/Cas9-mediated targeted chromosome elimination |
title_fullStr | CRISPR/Cas9-mediated targeted chromosome elimination |
title_full_unstemmed | CRISPR/Cas9-mediated targeted chromosome elimination |
title_short | CRISPR/Cas9-mediated targeted chromosome elimination |
title_sort | crispr/cas9-mediated targeted chromosome elimination |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701507/ https://www.ncbi.nlm.nih.gov/pubmed/29178945 http://dx.doi.org/10.1186/s13059-017-1354-4 |
work_keys_str_mv | AT zuoerwei crisprcas9mediatedtargetedchromosomeelimination AT huoxiaona crisprcas9mediatedtargetedchromosomeelimination AT yaoxuan crisprcas9mediatedtargetedchromosomeelimination AT huxinde crisprcas9mediatedtargetedchromosomeelimination AT sunyidi crisprcas9mediatedtargetedchromosomeelimination AT yinjianhang crisprcas9mediatedtargetedchromosomeelimination AT hebingbing crisprcas9mediatedtargetedchromosomeelimination AT wangxing crisprcas9mediatedtargetedchromosomeelimination AT shilinyu crisprcas9mediatedtargetedchromosomeelimination AT pingjie crisprcas9mediatedtargetedchromosomeelimination AT weiyu crisprcas9mediatedtargetedchromosomeelimination AT yingwenqin crisprcas9mediatedtargetedchromosomeelimination AT weiwei crisprcas9mediatedtargetedchromosomeelimination AT liuwenjia crisprcas9mediatedtargetedchromosomeelimination AT tangcheng crisprcas9mediatedtargetedchromosomeelimination AT liyixue crisprcas9mediatedtargetedchromosomeelimination AT hujiazhi crisprcas9mediatedtargetedchromosomeelimination AT yanghui crisprcas9mediatedtargetedchromosomeelimination |