BE4max Cytosine Base Editor
Optimized cytosine base editor with 1.8× higher efficiency than BE4. Enhanced nuclear import and codon optimization boost C-to-T conversion.
Origin: Codon-optimized rat APOBEC1 with enhanced nuclear localization signals
Characteristics
Editing efficiency 4.2-6× higher than BE4 at low plasmid doses through improved expression. Dual UGI domains maintain product purity with <1% indel formation. Active editing window positions 4-8 from PAM.
Applications: Current standard for high-efficiency C-to-T editing across diverse applications. Particularly effective in primary cells and hard-to-transfect cell types requiring lower plasmid doses. Widely validated for correcting pathogenic SNPs in mammalian systems.
Limitations: Large size (~5.8 kb coding sequence) challenges AAV packaging requiring split-intein or dual-vector strategies. Potential RNA off-target effects at high expression levels. Codon optimization may reduce performance in non-mammalian systems.
Architecture: Codon-optimized BE3 with two UGI domains for enhanced product stability. Additional nuclear localization signals improve nuclear import. Enhanced architecture reduces indel formation.
References
- Komor et al. (2016). Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature - Komor 2016 BE3
- 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
- Koblan et al. (2018). Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat Biotechnol - Koblan 2018 BE4max