Functional proteins with limited homology to natural proteins are designed using a large language model.

CLASH is a CRISPR-based platform that enables the parallel knock-in via homology-directed repair of a large pool of transgene variants encoded in adeno-associated virus vectors. CLASH can be applied to the systematic and unbiased selection of favorable features in T cells and, in principle, other cell types.

Targeted RNA degradation remains a challenge using existing methods owing to off-target effects and toxicity. We adapted the CRISPR-Csm complex, a multi-protein effector from type III CRISPR systems, for precise knockdown of nuclear or cytoplasmic transcripts in eukaryotic cells with minimal side effects.

Sequencing of proteins is a technically difficult task that typically requires digestion into short peptides before detection and identification. We developed a digestion-free method to chemically unfold and ‘scan’ full-length proteins through a nanopore, producing electrical fingerprints unique to individual protein molecules that are useful in their identification.