期刊文献

Enhancement of prime editing via xrRNA motif-joined pegRNA 收藏

通过XRRNA图案加入PEGRNA的素数编辑增强

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作者

Zhang; Guiquan[1];Liu; Yao[2];Huang; Shisheng[3];Qu; Shiyuan[3];Cheng; Daolin[1];Yao; Yuan[4];Ji; Quanjiang[5];Wang; Xiaolong[2];Huang; Xingxu[3];Liu; Jianghuai[1]

作者单位

[1]State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center at Medical School of Nanjing University, Nanjing, China;[2]Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China;[3]Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai, China;[4]Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, China;[5]School of Physical Science and Technology, ShanghaiTech University, Shanghai, China

关键词

CRISPR-Cas9 genome editing;Science;Humanities;Social Sciences;multidisciplinary

关键词译文

CRISPR-CAS9基因组编辑；科学；人文学科；社会科学；多学科

发布日期

06 April 2022

页码

1-12

DOI

10.1038/s41467-022-29507-x

来源信息

Scientific reports ISSN：2045-2322, 2022年, 1-12页

摘要

The prime editors (PEs) have shown great promise for precise genome modification. However, their suboptimal efficiencies present a significant technical challenge. Here, by appending a viral exoribonuclease-resistant RNA motif (xrRNA) to the 3′-extended portion of pegRNAs for their increased resistance against degradation, we develop an upgraded PE platform (xrPE) with substantially enhanced editing efficiencies in multiple cell lines. A pan-target average enhancement of up to 3.1-, 4.5- and 2.5-fold in given cell types is observed for base conversions, small deletions, and small insertions, respectively. Additionally, xrPE exhibits comparable edit:indel ratios and similarly minimal off-target editing as the canonical PE3. Of note, parallel comparison of xrPE to the most recently developed epegRNA-based PE system shows their largely equivalent editing performances. Our study establishes a highly adaptable platform of improved PE that shall have broad implications.

摘要译文

Prime编辑（PES）对精确的基因组修饰显示了巨大的希望。但是，他们的次优效率提出了重大的技术挑战。在这里，通过将耐病毒驱虫核酸酶的RNA图案（XRRNA）附加到PEGRNA的3'延伸部分，以提高对降解的耐药性，我们开发了升级的PE平台（XRPE），具有大大提高的多个细胞系中的编辑效率。在给定的细胞类型中，对于基本转换，小缺失和小插入，观察到给定细胞类型中最高3.1-，4.5和2.5倍的平均平均值增强。此外，XRPE表现出可比的编辑：indel比率和类似的最小脱靶编辑，与规范的PE3相似。值得注意的是，XRPE与最近开发的基于Epegrna的PE系统的并行比较显示了它们在很大程度上等效的编辑性能。我们的研究建立了一个高度适应性的改进的PE平台，具有广泛的影响。

Zhang; Guiquan[1];Liu; Yao[2];Huang; Shisheng[3];Qu; Shiyuan[3];Cheng; Daolin[1];Yao; Yuan[4];Ji; Quanjiang[5];Wang; Xiaolong[2];Huang; Xingxu[3];Liu; Jianghuai[1]. Enhancement of prime editing via xrRNA motif-joined pegRNA[J]. Scientific reports, 2022: 1-12