C-to-G Base Editor

C-to-G transversion base editor expanding beyond transition mutations. Enables targeted C-to-G conversion addressing 11-40% of disease SNPs.

Length: 1000 bp(333 aa)

Type: C-to-G Base Editor

Conversion: C-to-G

Editing window: Positions 4-8

Origin: Engineered APOBEC1 variants or R33A mutant with uracil DNA glycosylase

Architecture

Cytosine base editor fused with uracil DNA glycosylase (UNG) instead of UGI. UNG excises deaminated uracil, creating abasic site that is repaired to G opposite template C.

Characteristics

Achieves 5-30% C-to-G editing efficiency depending on sequence context and architecture. Requires cellular base excision repair pathway for transversion outcome. Multiple architectures available: CGBE1 with eUNG, or rXRCC1/Polβ fusion variants.

Applications

Enables C-to-G transversions correcting disease mutations inaccessible to transition base editors. Particularly effective in AT-rich sequence contexts. Expands therapeutic scope when combined with CBE/ABE to address 40% of ClinVar disease SNVs.

Limitations

Lower efficiency (5-30%) than transition base editors with higher sequence dependence. Byproduct indels more common than CBE/ABE systems. Product purity variable; C-to-A and C-to-T byproducts require careful optimization for specific targets.

Literature References

  1. Kurt et al. (2020). CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat Biotechnol - Kurt 2020 CGBE1
  2. Chen et al. (2021). Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins. Nat Commun - Chen 2021 CGBE
  3. Koblan et al. (2021). Efficient C•G-to-G•C base editors developed using CRISPRi screens, target-library analysis, and machine learning. Nat Biotechnol - Koblan 2021 CGBE Suite