Overview
- Researchers used a hybrid design that combined the ESM-IF1 inverse-folding model with evolution-informed residue constraints to generate new variants of the compact TnpB nuclease.
- The team screened the AI-designed proteins, called SynTnpBs, first in bacteria and then tested top candidates in plant and human cells to assess editing activity.
- The paper, which published on Thursday, July 16, 2026, reports many SynTnpBs matched or exceeded the activity of natural TnpB enzymes across those cell types.
- Cryo-electron microscopy of the most sequence-divergent SynTnpBs revealed new electrostatic and hydrogen-bond networks at the RNA–DNA interface that stabilize active conformations.
- Next steps include systematic specificity and safety profiling, broader functional tests for research and agricultural use, and consideration of regulatory pathways for any clinical or commercial applications.