ABE8e Adenine Base Editor
Enhanced ABE with 590-fold faster deamination than ABE7.10. PACE evolution enables 1.5-3× improved efficiency with broader editing window.
Origin: E. coli TadA-8e (phage-assisted continuous evolution with 8 additional mutations)
Characteristics
Catalytic activity 590-fold higher than ABE7.10 enabling editing at positions 4-9. Highly processive editing benefits multiplex applications and regulatory region disruption. Compatible with diverse Cas9 and Cas12 variants expanding targeting scope.
Applications
High-efficiency A-to-G editing at challenging loci poorly edited by ABE7.10. Achieves 98-99% target modification in primary human T cells for therapeutic applications. Efficiently installs HPFH mutations and corrects disease mutations in BCL11A enhancer and HBG promoters.
Limitations
Broader editing window (positions 4-9) increases bystander editing at adjacent adenines. Modest increase in Cas9-dependent and -independent off-target DNA editing. Elevated transcriptome-wide RNA editing ameliorated by V106W mutation variant.
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
- Richter et al. (2020). Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat Biotechnol - Richter 2020 ABE8e
- Gaudelli et al. (2020). Directed evolution of adenine base editors with increased activity and therapeutic application. Nat Biotechnol - Gaudelli 2020 ABE8 Variants