Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain.

Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain.
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DOI:
10.1038/s41467-021-25928-2
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发表时间:
2021-09-23
影响因子:
16.6
通讯作者:
Kim HH
Kim HH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Song M;Lim JM;Min S;Oh JS;Kim DY;Woo JS;Nishimasu H;Cho SR;Yoon S;Kim HH

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尽管PRIME编辑是一种很有前途的基因组编辑方法,但是PRIME编辑者2(PE2)的效率往往是不够的。在这里,我们通过添加RAD51DNA结合域来生成PE2的一个更有效的变体,称为hyPE2。当在内源位点测试时,HyPE2的效率中位数是PE2的1.5倍或1.4倍(范围为0.99到2.6倍);此外,在PE2诱导的原始编辑效率非常低的站点(效率 < 1%),HyPE2能够使原始编辑在高达34%的目标序列上的效率从1.1%到2.9%不等,潜在地促进了原始编辑应用。虽然优质编辑是一项很有前途的技术,但PE2系统的效率往往很低。在这里,作者融合了RAD51 DNA结合域,以创建hyPE2,提高了编辑效率。
Although prime editing is a promising genome editing method, the efficiency of prime editor 2 (PE2) is often insufficient. Here we generate a more efficient variant of PE2, named hyPE2, by adding the Rad51 DNA-binding domain. When tested at endogenous sites, hyPE2 shows a median of 1.5- or 1.4- fold (range, 0.99- to 2.6-fold) higher efficiencies than PE2; furthermore, at sites where PE2-induced prime editing is very inefficient (efficiency < 1%), hyPE2 enables prime editing with efficiencies ranging from 1.1% to 2.9% at up to 34% of target sequences, potentially facilitating prime editing applications. While prime editing is a promising technology, PE2 systems often have low efficiency. Here the authors fuse a Rad51 DNA-binding domain to create hyPE2 with improved editing efficiency.
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