Hyperactive nickase activity improves adenine base editing

Base editing technologies enable programmable single-nucleotide changes in target DNA without double-stranded DNA breaks. Adenine base editors (ABEs) allow for precise conversion of adenine (A) to guanine (G). However, limited availability of optimized deaminases as well as variability of deamination efficiencies across different target sequences can limit the ability of ABEs to achieve effective adenine editing. Here, we explored the use of a TurboCas9 nickase in an ABE to improve its deamination activity. The resulting TurboABE exhibits amplified deamination rates on a variety of adenine target sites without increasing off-target editing in DNA and RNA. An interesting feature of TurboABE is its ability to significantly improve the deamination activity of bases with normally low deamination rates in the editing window of each target DNA. Development of improved ABEs provides new possibilities for precise genetic modification of genes in living cells.