https://scholars.lib.ntu.edu.tw/handle/123456789/639112
標題: | Whole genomic analysis reveals atypical non-homologous off-target large structural variants induced by CRISPR-Cas9-mediated genome editing | 作者: | Tsai, Hsiu-Hui Kao, Hsiao-Jung Kuo, Ming-Wei CHIN-HSIEN LIN Chang, Chun-Min Chen, Yi-Yin Chen, Hsiao-Huei Kwok, Pui-Yan Yu, Alice L Yu, John |
公開日期: | 十二月-2023 | 卷: | 14 | 期: | 1 | 起(迄)頁: | 5183 | 來源出版物: | Nature communications | 摘要: | CRISPR-Cas9 genome editing has promising therapeutic potential for genetic diseases and cancers, but safety could be a concern. Here we use whole genomic analysis by 10x linked-read sequencing and optical genome mapping to interrogate the genome integrity after editing and in comparison to four parental cell lines. In addition to the previously reported large structural variants at on-target sites, we identify heretofore unexpected large chromosomal deletions (91.2 and 136 Kb) at atypical non-homologous off-target sites without sequence similarity to the sgRNA in two edited lines. The observed large structural variants induced by CRISPR-Cas9 editing in dividing cells may result in pathogenic consequences and thus limit the usefulness of the CRISPR-Cas9 editing system for disease modeling and gene therapy. In this work, our whole genomic analysis may provide a valuable strategy to ensure genome integrity after genomic editing to minimize the risk of unintended effects in research and clinical applications. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/639112 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-023-40901-x |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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