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

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

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