A motif preferred adenine base editor with minimal bystander and off-targets editing

Oct 15, 2025Nature communications

A targeted adenine base editor with low unintended and off-target changes

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Abstract

47% of hereditable diseases are caused by single C•G-to-T•A base conversions.

  • Efficient A-to-G base editing tools could significantly impact the treatment of hereditable diseases.
  • ABE8e-YA shows an average A-to-G editing efficiency improvement of up to 3.1-fold compared to ABE3.1.
  • This new tool maintains reduced bystander C editing and minimizes off-target events in DNA or RNA.
  • ABE8e-YA effectively corrects pathogenic mutations in human cells, addressing 9.3% of pathogenic point mutations.
  • In vivo applications include the generation of mouse models for hypocholesterolemia and tail loss, as well as base editing for hypercholesterolemia gene therapy.

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Key numbers

3.1×
Increase in Efficiency
Average efficiency increase of compared to ABE3.1.
9.3%
Addressed
Percentage of point mutations suitable for correction using .

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