Nature biotechnology

Designed enzymes allow precise DNA changes from A to G

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated

Abstract

snuABE achieved a median efficiency of 5.4% in A-to-G editing across 32 targets in HEK293T cells.

  • snuABE is designed to minimize bystander nucleotide conversions, enhancing precision in base editing.
  • The technology utilizes a nickase Cas9 fused with the deaminase domain of ADAR, targeting DNA:RNA hybrids.
  • A target-adenine guide RNA (tagRNA) creates a mismatch at the target adenine, facilitating specific editing.
  • Engineering ADAR using EvolvePro improved snuABE activity significantly, achieving a maximum efficiency of 50.0%.
  • No detectable DNA off-target editing was observed at predicted off-target or orthogonal R-loop sites.

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Funding

Competing interests

Competing interests: H.W.I., B.J. and S.B. have filed a patent application related to this work. The other authors declare no competing interests.
PubMed

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