Abes

Adenine base editors (ABEs) are a class of programmable genome editing tools that enable the direct conversion of an A-T base pair to a G-C base pair in genomic DNA without introducing double-strand breaks.

ABEs typically consist of a catalytically impaired CRISPR-associated nuclease, such as a nickase Cas9, fused to an engineered adenine deaminase. Guided by a single-guide RNA, the complex binds a targeted DNA sequence, where the deaminase converts adenine to inosine within a defined editing window. During DNA replication or repair, inosine is read as guanine, resulting in an A•T to G•C substitution. The nickase component can introduce a nick in the non-edited strand to bias repair toward the desired base pair.

The first successful ABEs were reported in 2017, demonstrating efficient A-to-G edits without creating double-strand breaks. Since then, newer variants with higher activity and expanded targeting range have been developed, including improved TadA variants and Cas9 variants that recognize a broader set of PAMs. This broadens the range of accessible genomic sites for editing.

Applications of ABEs span basic research and potential therapeutic contexts. They have been used to study gene function in mammalian cells, plants, and model organisms, and hold promise for correcting disease-causing mutations that require A•T to G•C changes. Compared with nuclease-based approaches, ABEs minimize double-strand break–associated indels but can still produce off-target edits, including unintended edits at non-target adenines and some RNA edits.

Limitations and safety considerations include editing window constraints, potential off-target activity, immunogenicity of editing enzymes, and delivery challenges. As of the mid-2020s, ABEs are not yet approved for clinical therapy, and ongoing research continues to assess efficacy, specificity, and ethical implications.