AAV-optimized cytosine base editor with enhanced nuclear localization and codon usage. Enables dual-AAV delivery for in vivo therapeutic applications.
Length: 2730 bp(910 aa)
Type: Cytosine Base Editor
Conversion: C-to-T
Editing window: Positions 4-8
Origin: Optimized rat APOBEC1, split via Npu intein (E573/C574)
Characteristics
Comparable efficiency to BE4max with optimization for AAV packaging via split-intein reconstitution. Achieves 38-59% editing in mouse tissues (brain, liver, retina) following systemic or local AAV delivery. Split design enables packaging within 4.7 kb AAV capacity limit.
Applications: In vivo therapeutic base editing delivered via dual-AAV vectors. Validated across multiple organs including brain, liver, retina, heart, and skeletal muscle. Successfully corrected Niemann-Pick disease type C mutation in mice, extending lifespan and reducing neurodegeneration.
Limitations: Requires dual-AAV vector system increasing manufacturing complexity and cost. Split-intein reconstitution efficiency may vary by tissue and AAV serotype. Lower editing efficiency than single-vector systems in some contexts.
Architecture: Split BE4max variant optimized for dual-AAV delivery with Npu intein reconstitution system
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
Levy et al. (2020).
Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses.
Nat Biomed Eng - Levy 2020 BE3.9max
Koblan et al. (2018).
Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction.
Nat Biotechnol - Koblan 2018 BE4max
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