Hyperactive Nickase\nActivity Improves Adenine Base\nEditing

Base editing technologies enable\nprogrammable single-nucleotide\nchanges in target DNA without double-stranded DNA breaks. Adenine\nbase editors (ABEs) allow precise conversion of adenine (A) to guanine\n(G). However, limited availability of optimized deaminases as well\nas their variable efficiencies across different target sequences can\nlimit the ability of ABEs to achieve effective adenine editing. Here,\nwe explored the use of a TurboCas9 nickase in an ABE to improve its\ngenome editing activity. The resulting TurboABE exhibits amplified\nediting efficiency on a variety of adenine target sites without increasing\noff-target editing in DNA and RNA. An interesting feature of TurboABE\nis its ability to significantly improve the editing frequency at bases\nwith normally inefficient editing rates in the editing window of each\ntarget DNA. Development of improved ABEs provides new possibilities\nfor precise genetic modification of genes in living cells.