Design of highly functional genome editors by modelling CRISPR–Cas sequences

Ruffolo et al. (2025). Nature DOI: 10.1038/s41586-025-09298-z Citations: 136

Key findings

First AI-designed CRISPR editor (OpenCRISPR-1, 1,380 aa) generated entirely by large language models trained on >1 million CRISPR operons. Achieved comparable on-target activity to SpCas9 (median indel rates 56.4% vs 47.1%) with 95% reduction in off-target editing (0.32% vs 6.1%). OpenCRISPR-1 is 403 mutations from SpCas9 and 182 mutations from any natural CRISPR protein.