Department of Chemistry, Hanyang University, Seoul, South Korea.
Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea.
Nat Biotechnol. 2019 Oct;37(10):1145-1148. doi: 10.1038/s41587-019-0254-4. Epub 2019 Sep 23.
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.
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。