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 precise conversion of adenine (A) to guanine
(G). However, limited availability of optimized deaminases as well
as their variable 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
genome editing activity. The resulting TurboABE exhibits amplified
editing efficiency 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 editing frequency at bases
with normally inefficient editing 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.