QBEmax is a sequence-permuted and internally protected base editor

Nat Biotechnol. 2026 Mar;44(3):387-393. doi: 10.1038/s41587-025-02641-9. Epub 2025 Apr 21.

Abstract

Cytosine base editors (CBEs) show promise for multiplex gene knockout applications, but impure edits, indels and off-targets still frequently occur. We describe here QBEmax, which exhibits high efficiency, low indel and off-targets and high product purity with up to 99.8% of edits comprised of C-to-T. Through molecular dynamic modeling, QBEmax presents as a compact and stable base editor that shields protected bases from undesired repair processes.

MeSH terms

  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Cytosine* / chemistry
  • Gene Editing* / methods
  • Humans
  • INDEL Mutation
  • Molecular Dynamics Simulation

Substances

  • Cytosine