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| Title | De novo design of potent CRISPR-Cas13 inhibitors. |
|---|---|
| Journal, issue, pages | Nat Chem Biol, Year 2026 |
| Publish date | Jan 26, 2026 |
Authors | Cyntia Taveneau / Her Xiang Chai / Jovita D'Silva / Rebecca S Bamert / Honglin Chen / Brooke K Hayes / Roland W Calvert / Jacob Purcell / Daniel J Curwen / Fabian Munder / Lisandra L Martin / Jeremy J Barr / Joseph Rosenbluh / Mohamed Fareh / Rhys Grinter / Gavin J Knott / ![]() |
| 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 ...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. |
External links | Nat Chem Biol / PubMed:41588195 |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 1.94 - 3.43 Å |
| Structure data | EMDB-48668, PDB-9mvs: ![]() PDB-9mvr: |
| Chemicals | ![]() ChemComp-CL: ![]() ChemComp-HOH: |
| Source |
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Keywords | DE NOVO PROTEIN / anti-CRISPR / Acr / CRISPR / Cas13 / DE NOVO PROTEIN/HYDROLASE/RNA / de novo / DE NOVO PROTEIN-HYDROLASE-RNA complex |
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leptotrichia buccalis (bacteria)
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