New protein engineering method yields compact genome editor with 97 percent peak efficiency
A team published EvoMax, a model-guided protein engineering strategy, in Nature Biotechnology to optimize compact eukaryotic Fanzor2 nucleases. The method combines Gaussian process regression, protein language models and inverse folding to navigate sequence-to-fitness landscapes. Researchers generated an engineered variant called FanzMAX v3-hLa that hit 97 percent editing efficiency at its best-performing endogenous locus. Across 19 endogenous mammalian loci, the variant averaged 33 percent efficiency. It outperformed established compact genome editors enNlovFz2 and enCnCas12f1 by more than 2.6-fold. The team also demonstrated in vivo editing of the hPCSK9 gene in humanized mice.
EvoMax offers a way to engineer proteins when large mutational datasets are not available. The optimized editor showed effective target site editing in mammalian cells and in live mice.
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