Ancestral BE4max Cytosine Base Editor

Advanced CBE using ancestral APOBEC reconstruction. Minimized transcriptome-wide off-targets with narrower editing window and lower toxicity.

Length: 1000 bp (333 aa)

Type: Cytosine Base Editor

Conversion: C-to-T

Origin: Anc689 ancestral APOBEC1 (36 amino acid substitutions from 468 homolog reconstruction)

Characteristics

Editing efficiency comparable to BE4max with improved on-target performance at low doses (1.7-9× vs BE4). Narrower editing window at positions 5-6 reduces bystander mutations. Enhanced specificity through structure-guided ancestral sequence reconstruction.

Applications

High-priority therapeutic applications requiring enhanced safety profile and reduced off-target effects. Optimal for targets where narrow editing window provides precision advantage. Particularly effective in contexts requiring lower expression levels or transient delivery.

Limitations

Narrower editing window (positions 5-6) may exclude some target sites accessible to BE3/BE4max. Performance advantages most pronounced at suboptimal plasmid doses. May require empirical testing against BE4max for specific applications.

Literature References

  1. Komor et al. (2016). Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature - Komor 2016 BE3
  2. Komor et al. (2017). Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci Adv - Komor 2017 BE4
  3. Koblan et al. (2018). Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol - Koblan 2018 BE4max