AlphaFold-guided tweaks reduce CRISPR off-target edits while preserving accuracy
Researchers used AlphaFold to map Cas9’s interactions with on- and off-target DNA and pinpoint amino acids responsible for mispairing. By swapping 23 residues at 10 key positions, they produced Cas9 variants with substantially lower off-target editing (down from 28% to 5%) without sacrificing on-target activity, demonstrating a general approach to tailor gene-editing tools and potentially guide broader protein-DNA engineering.