OpenCRISPR-1 Nuclease

Characteristics

First fully AI-designed CRISPR nuclease created by large language models trained on >1 million CRISPR operons. Comparable on-target activity to SpCas9 (56.4% vs 47.1% median indel rates) with 95% reduction in off-target editing (0.32% vs 6.1%). 403 mutations from SpCas9 and 182 mutations from any natural CRISPR protein. Compatible with canonical SpCas9 sgRNAs and standard base editing architectures. Lacks immunodominant SpCas9 T cell epitopes, suggesting reduced immunogenicity. Blunt-end double-strand breaks. Strict NGG PAM requirement provides enhanced specificity - minimal activity at non-NGG PAMs.

Literature References

1. Ruffolo et al. (2025). Design of highly functional genome editors by modelling CRISPR–Cas sequences. Nature - Ruffolo 2025 OpenCRISPR