1483-Structure-Guided Design of Minimal RNA-Guided Nucleases
Researchers have developed a novel protein design strategy to create synthetic RNA-guided nucleases, known as SynTnpBs, which diverge significantly from natural evolutionary sequences. By combining inverse-folding AI models with evolutionary data to preserve essential DNA and RNA binding sites, the team successfully engineered complex, multidomain enzymes with high catalytic activity. High-throughput screening identified several artificial variants that match or surpass wild-type performance in bacterial, plant, and human cells. Structural analysis via cryo-electron microscopy confirmed that…
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