🧵6/6 And we resolved a previously unobserved TAM-bound state providing further mechanistic insights!

🧵5/6 We solved the first experimental structures of an AI-designed RNA-guided nuclease, which revealed new protein-nucleic acid contacts across conformational states.

🧵4/6 Some of our synthetic gene editors exceeded natural proteins in activity while being equally specific.

🧵3/6 We assessed activity using a high-throughput bacterial assay, followed by editing the human and plant genomes 🧫🌱

🧵2/6 By coupling inverse folding with protein and DNA/RNA evolutionary conservation, we achieved a high design success rate ⚙️

We programmed CRISPR-Cas12a2 to recognize cancer mutations, especially in TP53, and selectively kill mutant cells through transcript-activated chromatin shredding.

🧵4/4 We solved the first experimental structure of an AI-designed RNA-guided nuclease, which revealed new protein-nucleic acid contacts across conformational states. 🔗 See our preprint: www.biorxiv.org/content/10.6...

🧵3/4 We assessed activity using a high-throughput bacterial assay, followed by editing the human and plant genomes 🧫🌱

🧵2/4 By coupling inverse folding with evolutionary information, we generated highly active and diverse variants with a high design success rate ⚙️

"Jane Goodall showed us what a life in science could look like: rigorous discovery paired with fierce advocacy for what you study. She gave the world six decades of groundbreaking research on chimpanzees and their habitats, then turned that knowledge into a global movement for conservation." (1/2)