Adenine base editor (Cas9 nickase–TadA fusion protein) (ABE)

The adenine base editor (ABE) is a synthetic genome editing protein complex consisting of an engineered tRNA adenine deaminase (TadA) fused to a Cas9 nickase (nCas9) and guided by a specific single-guide RNA (sgRNA). Upon binding to a user-specified genomic DNA sequence, the ABE catalyzes the deamination of adenine to inosine (A→I), which is interpreted by DNA polymerase as guanine during replication or repair, resulting in the permanent conversion of A•T to G•C base pairs at the targeted genomic locus. This process achieves precise, programmable, single-nucleotide changes in DNA without generating double-stranded breaks or requiring a donor DNA template, and is widely used for research and developing therapeutics to correct disease-causing point mutations. The evolved TadA domain in ABEs enables DNA (rather than RNA) adenine deamination and is typically paired with wild-type TadA in a heterodimer for optimal activity[1][2][3][6]. ABEs have advanced through several generations to improve efficiency and reduce off-target effects but remain subject to concerns about specificity, off-target DNA and RNA editing, and delivery for therapeutic use[3][4][7].

Other names

Adenine base editorABECRISPR–Cas9 adenine base editorCas9 nickase–TadA fusion proteinnCas9–TadA ABE

Guide RNA–directed targeting of genomic loci followed by adenine deamination (A→I, interpreted as G) on DNA, resulting in precise A•T to G•C base conversions without generating double-stranded breaks[1][3][6].