Cytosine base editors induce off-target mutations and adverse phenotypic effects in transgenic mice

文献类型： 外文期刊

第一作者： Yan, Nana

作者： Yan, Nana;Feng, Hu;Sun, Yongsen;Xin, Ying;Zhang, Haihang;Lu, Hongjiang;Zheng, Jitan;He, Chenfei;Zuo, Zhenrui;Yuan, Tanglong;Li, Nana;Xie, Long;Zuo, Erwei;Xin, Ying;Lu, Hongjiang;Li, Nana;Xin, Ying;Lu, Hongjiang;Li, Nana;Zheng, Jitan;Wei, Wu;Wei, Wu;Sun, Yidi

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：16.6； 五年影响因子：17.0 ）

ISSN：

年卷期： 2023 年 14 卷 1 期

页码：

收录情况： SCI

摘要： Base editors have been reported to induce off-target mutations in cultured cells, mouse embryos and rice, but their long-term effects in vivo remain unknown. Here, we develop a Systematic evaluation Approach For gene Editing tools by Transgenic mIce (SAFETI), and evaluate the off-target effects of BE3, high fidelity version of CBE (YE1-BE3-FNLS) and ABE (ABE7.10(F148A)) in similar to 400 transgenic mice over 15 months. Whole-genome sequence analysis reveals BE3 expression generated de novo mutations in the offspring of transgenic mice. RNA-seq analysis reveals both BE3 and YE1-BE3-FNLS induce transcriptome-wide SNVs, and the numbers of RNA SNVs are positively correlated with CBE expression levels across various tissues. By contrast, ABE7.10(F148A) shows no detectable off-target DNA or RNA SNVs. Notably, we observe abnormal phenotypes including obesity and developmental delay in mice with permanent genomic BE3 overexpression during long-time monitoring, elucidating a potentially overlooked aspect of side effects of BE3 in vivo.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序