Using a protein-DNA language model to design precise and small adenine base editors

A protein-nucleic acid language model helped design a smaller, more precise adenine base editor with strong activity in preclinical systems.

Protein-engineering experiments produced PNLM-pcABE, a 27% smaller ABE8e variant with a 3-nt editing window, near-background off-target events in HEK293T cells, up to 133.5-fold precision improvement for pathogenic mutation correction, efficient zygote editing in albino mice, and reduced PCSK9 expression after LNP delivery in mice.

The results come from cells, zygote editing, and mouse delivery experiments, so therapeutic performance and safety in humans are not established.