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腺嘌呤碱基编辑器在人类细胞中催化胞嘧啶转化。

Adenine base editors catalyze cytosine conversions in human cells.

机构信息

Department of Chemistry, Hanyang University, Seoul, South Korea.

Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.

出版信息

Nat Biotechnol. 2019 Oct;37(10):1145-1148. doi: 10.1038/s41587-019-0254-4. Epub 2019 Sep 23.

Abstract

Adenine base editors comprise an adenosine deaminase, evolved in vitro, and a Cas9 nickase. Here, we show that in addition to converting adenine to guanine, adenine base editors also convert cytosine to guanine or thymine in a narrow editing window (positions 5-7) and in a confined TC*N sequence context. Adenine base editor-induced cytosine substitutions occur independently of adenosine conversions with an efficiency of up to 11.2% and reduce the number of suitable targeting sites for high-specificity base editing.

摘要

腺嘌呤碱基编辑器由体外进化的腺嘌呤脱氨酶和 Cas9 切口酶组成。在这里,我们表明,除了将腺嘌呤转化为鸟嘌呤外,腺嘌呤碱基编辑器还可以在狭窄的编辑窗口(位置 5-7)和受限的 TC*N 序列背景下将胞嘧啶转化为鸟嘌呤或胸腺嘧啶。腺嘌呤碱基编辑器诱导的胞嘧啶取代与腺嘌呤转化无关,效率高达 11.2%,并减少了高特异性碱基编辑的合适靶向位点数量。

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