N. meningitidis ABE8e Adenine Base Editor
Ultra-compact adenine base editor using Nme2Cas9 with N4CC PAM, enabling targeting of A-rich sequences.
Origin: TadA8e deaminase fused to Neisseria meningitidis Nme2Cas9 D16A nickase
Characteristics
Highly compact architecture using Nme2Cas9 enables single-AAV delivery with ample cargo space. Recognizes N4CC PAM (N = any nucleotide), providing access to A/T-rich genomic regions inaccessible to GC-rich PAM editors. Uses 24-nucleotide protospacer. Editing window spans positions 4-10. Part of three-editor suite collectively targeting ~82% of genomic adenines.
Applications: Single-AAV base editing of A/T-rich genomic regions. Complementary to SaCas9 and CjCas9 editors for comprehensive genome coverage. Suitable for targets with N4CC PAMs where other compact editors cannot access. Enables multi-editor therapeutic strategies for maximum targeting flexibility.
Limitations: N4CC PAM restricts targeting to specific sequence contexts. Narrower editing window (positions 4-10) compared to some ABE variants. Lower targeting scope than relaxed PAM editors when considered individually, though complementary to other editors in suite.
Architecture: All-in-one (single vector)
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
- Davis et al. (2022). Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors. Nat Biomed Eng - Davis 2022 Single-AAV ABEs