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This work found that the ABEs were fully described by the single dimension of intrinsic deaminase activity with no evidence for independent specialization with respect to local sequence context, editing window width, RNA editing, RNA editing, or genotoxicity.
A protein design strategy is used that couples a structure-guided inverse-folding model with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12-like nuclease, termed SynTnpBs, establishing a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.
ProteinGuide is applied jointly with wet-lab data generation to increase the editing activity of an adenine base editor in vivo, resulting in a base editor with higher editing efficiency than was previously achieved using seven rounds of directed evolution.
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