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
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.
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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