Increase base editing efficiency and product variety through fusion of Cas9 nickase to cytosine and adenosine deaminases

Base editors, which are created through fusion of Cas9 nickase to either cytidine or adenine deaminase, efficiently catalyze site-specific nucleotide conversions with minimal indel rates1, 2. However, cytidine base editor (CBE) or adenine base editor (ABE) is able to only generate base conversion on single nucleotide type which limits the product multiplicity. Here we show that through fusion of cytidine and adenine deaminases with Cas9n, a novel cytidine-adenine base editor (ACBE) was developed. ACBE is able to generate C>T and A>G conversions in the same allele.

碱基编辑器（Base editors）通过将Cas9切口酶（Cas9 nickase）与胞嘧啶脱氨酶（cytidine deaminase）或腺嘌呤脱氨酶（adenine deaminase）融合构建而成，可高效催化位点特异性核苷酸转换，且插入缺失率极低[1,2]。然而，胞嘧啶碱基编辑器（CBE）或腺嘌呤碱基编辑器（ABE）仅能实现单一种类碱基的转换，这限制了产物的多样性。本研究表明，通过将胞嘧啶脱氨酶与腺嘌呤脱氨酶共同与Cas9n融合，我们开发出一种新型胞嘧啶-腺嘌呤碱基编辑器（ACBE）。ACBE可在同一等位基因上同时实现C>T与A>G的碱基转换。