Disabling Cas9 by an anti-CRISPR DNA mimic

Jul 15, 2017Science advances

Stopping Cas9 activity using a DNA-like anti-CRISPR molecule

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Abstract

A 3.9 Å resolution structure reveals that the anti-CRISPR protein AcrIIA4 binds specifically to Cas9-sgRNA complexes.

  • AcrIIA4 only attaches to assembled Cas9-sgRNA complexes and not to Cas9 alone.
  • The binding of AcrIIA4 occurs at a specific site on Cas9 that typically interacts with DNA.
  • AcrIIA4 can inhibit DNA recognition by Cas9 but does not affect already formed Cas9-sgRNA-DNA complexes.
  • Delivering AcrIIA4 into human cells allows for targeted gene editing by Cas9 while minimizing unintended edits.
  • These findings enhance understanding of how AcrIIA4 functions as an inhibitor of CRISPR-Cas9 gene editing.

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