AlphaFold-guided tweaks reduce CRISPR off-target edits while preserving accuracy

TL;DR Summary
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.
- Team uses AlphaFold AI to redesign gene-editing proteins to make them safer Ars Technica
- Nobel Laureate Jennifer Doudna enters AI protein design arena Fierce Biotech
- AlphaFold AI redesigns gene-editing proteins to enhance safety, and biotech investors should pay attention Crypto Briefing
- AI‑designed gene‑editing enzymes expand the CRISPR toolbox Phys.org
- AI Redesigns Minimal CRISPR Nucleases CRISPR Medicine News
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