Engineering of near-PAMless adenine base editor with enhanced editing activity and reduced off-target

Jun 6, 2022Molecular therapy. Nucleic acids

Improved adenine base editor that works with fewer DNA restrictions, edits better, and causes fewer unintended changes

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Abstract

47% of pathogenic point mutations may be corrected by ABE-induced A·T-to-G·C conversions.

  • A new adenine base editor, CE-8e-SpRY, shows improved editing activity at NRN PAMs compared to NYN PAMs.
  • CE-8e-SpRY is capable of targeting nearly all genomic sites and exhibits the highest targeting efficiency among tested SpRY-based adenine base editors.
  • This editor demonstrates reduced off-targeting effects in both RNA and DNA.
  • With optimized guide RNAs, CE-8e-SpRY can achieve efficient editing at specific disease-related sites that conventional adenine base editors cannot.

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