We developed Protein2PAM, an evolution-informed protein language model that predicts protospacer-adjacent motif (PAM) specificity of CRISPR–Cas enzymes.
We developed Protein2PAM, an evolution-informed protein language model that predicts protospacer-adjacent motif specificity of CRISPR–Cas enzymes. Using in silico mutagenesis and model-guided evolution, we generated Cas9 variants with broadened PAM compatibility and higher activity, enabling editing of genomic sites that were previously inaccessible owing to PAM recognition constraints.
A review article that examines progress toward developing PAM-free CRISPR–Cas nucleases and proposes an alternative approach that leverages a repertoire of PAM-specific nucleases.This paper reports the engineering of SpCas9 variants with altered PAM specificities, using structure-guided design, directed evolution and combinatorial mutagenesis.This paper reports the creation of AI-designed CRISPR gene editors that perform precise human genome editing and rival natural Cas9 enzymes.This paper reports the discovery of natural PAM diversity across 79 Cas9 orthologs, uncovering dozens of distinct PAM requirements that together expand the potential genome-editing toolkit.
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