Team uses AlphaFold AI to redesign gene-editing proteins to make them safer
Summary
Ars Technica reports on a Nature paper where AlphaFold was used to map how Cas9 off-target interactions occur and guide design of safer gene-editing proteins. The study identifies key Cas9 regions that change contacts with RNA at off-target sites and demonstrates 23 amino-acid swaps that reduce off-target editing from 28% to 5% while maintaining on-target activity. The work proposes a general approach called ContactSeek for tuning protein-DNA interactions, with potential applications beyond gene editing.