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Precise, minimally evolved adenine base editors generated through mutation reversion analysis - PubMed

3 hours ago
  • #TadA
  • #ABEs
  • #gene-editing
  • Adenine base editors (ABEs) enable A•T to G•C base pair changes in the genome.
  • Initial ABE development involved directed evolution, introducing 14 mutations into TadA to create ABE7.10.
  • Mutation reversion analysis categorized mutations as critical, dispensable, or host-dependent.
  • Up to five mutations can be reverted to wild type, creating minimally evolved ABEs (ME-ABEs).
  • ME-ABEs show narrow editing windows, enhanced on-target editing, and low off-target activity.
  • ME-ABEs efficiently edit six clinically challenging sites that were problematic for ABE7.10, ABE8e, or ABE8.20.
  • A.C.K. has disclosed conflicts of interest related to patents and equity in biotech companies.