Target-AID Cytosine Base Editor

Alternative cytosine base editor using sea lamprey cytidine deaminase. Narrower editing window (positions 2-4) with reduced cellular toxicity.

Length: 1000 bp(333 aa)

Type: Adenine Base Editor

Conversion: A-to-G (via C-to-T intermediate)

Editing window: Positions 2-4 (narrower)

Origin: Sea lamprey PmCDA1 cytidine deaminase

Characteristics

Narrow editing window at positions 2-4 upstream of PAM (18 bases from PAM). Lower efficiency than APOBEC1-based editors but useful when PAM placement is suboptimal. Functions through base excision repair pathway rather than direct replication.

Applications: Alternative C-to-T editing when ABE7.10 or BE3/BE4 PAM placement prevents targeting. Validated in yeast, mammalian cells, and plant systems with reduced toxicity. Effective for applications tolerating lower efficiency in exchange for reduced cellular stress.

Limitations: Lower editing efficiency compared to BE3/BE4 family at most targets. Editing window position further from PAM limits target site selection. Indirect mechanism via base excision repair increases variability in editing outcomes.

Architecture: PmCDA1 cytidine deaminase from sea lamprey fused to Cas9 D10A nickase. Deaminates cytosine on single-stranded DNA, indirectly creating A-to-G edits on opposite strand.

References

  1. Nishida et al. (2016). Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science - Nishida 2016 Target-AID