9MVR

AI-designed Cas13 anti-CRISPR AIcrVIA1

Summary for 9MVR

• Entry DOI: 10.2210/pdb9mvr/pdb
• Descriptor: AIcrVIA1, CHLORIDE ION (3 entities in total)
• Functional Keywords: anti-crispr, acr, crispr, cas13, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 19433.16

Authors

Taveneau, C.,Chai, H.X.,Knott, G.J. (deposition date: 2025-01-15, release date: 2026-02-25, Last modification date: 2026-04-29)

Primary citation

Taveneau, C.,Chai, H.X.,D'Silva, J.,Bamert, R.S.,Chen, H.,Hayes, B.K.,Calvert, R.W.,Purcell, J.,Curwen, D.J.,Munder, F.,Martin, L.L.,Barr, J.J.,Rosenbluh, J.,Fareh, M.,Grinter, R.,Knott, G.J.
De novo design of potent CRISPR-Cas13 inhibitors.
Nat.Chem.Biol., 2026

PubMed Abstract: CRISPR-Cas systems are transformative tools for gene editing that can be tuned or controlled by anti-CRISPRs (Acrs)-phage-derived inhibitors that regulate CRISPR-Cas activity. However, Acrs that can inhibit biotechnologically relevant CRISPR systems are relatively rare and challenging to discover. To overcome this limitation, we describe a highly successful and rapid approach that leverages de novo protein design to develop new-to-nature proteins for controlling CRISPR-Cas activity. Here, using Leptotrichia buccalis CRISPR-Cas13a as a representative example, we demonstrate that Acrs designed using artificial intelligence (AIcrs) are capable of highly potent and specific inhibition of CRISPR-Cas13a nuclease activity. We present a comprehensive workflow for design validation and demonstrate AIcr functionality in controlling CRISPR-Cas13 activity in bacterial and human cells. The ability to design bespoke inhibitors of Cas effectors will contribute to the ongoing development of CRISPR-Cas tools in diverse applications across research, medicine, agriculture and microbiology.

PubMed: 41588195
DOI: 10.1038/s41589-025-02136-3

Experimental method

X-RAY DIFFRACTION (1.94 Å)