N. meningitidis ABE8e Adenine Base Editor

Ultra-compact adenine base editor using Nme2Cas9 with N4CC PAM, enabling targeting of A-rich sequences.

Length: 3900 bp (1300 aa)

Type: Adenine Base Editor

Conversion: A-to-G

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.

Literature References

  1. 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
  2. Richter et al. (2020). Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat Biotechnol - Richter 2020 ABE8e
  3. 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