ABE7.10 Adenine Base Editor
First adenine base editor validated in human cells, achieving ~50% A-to-G conversion at positions 4–7 with ≤0.1% indels. Addresses the class of pathogenic mutations responsible for ~48% of disease-causing SNPs. Foundational reference for all subsequent ABE development, using an evolved TadA*–SpCas9 D10A nickase heterodimer.
Origin: E. coli TadA adenosine deaminase (evolved through 7 rounds of directed evolution)
Architecture
Evolved TadA deaminase (E. coli tRNA adenosine deaminase) fused to Cas9 D10A nickase. Heterodimer of wild-type TadA and evolved TadA* enables processive deamination.
Characteristics
Achieves ~50% A-to-G editing efficiency at positions 4-7 with >99.9% product purity. Heterodimer of wild-type TadA and evolved TadA* enables processive deamination. Indel formation typically ≤0.1% with minimal bystander editing.
Applications
Corrects A-to-G transition mutations addressing ~48% of known pathogenic SNPs. Complements cytosine base editors for all four transition mutations. Validated for installing disease-suppressing mutations and correcting hereditary disorders in human cells.
Limitations
Editing window positions 4-7 narrower than some applications require. Lower efficiency than ABE8e variants at challenging loci and in primary cells. Slower deamination kinetics can result in incomplete editing before Cas9 dissociates.
Sequence
Literature References
- Gaudelli NM, Komor AC, Rees HA, et al. (2017). Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551:464-471 - Gaudelli 2017 Adenine Base Editor