CRISPR-Cas Inhibiting Polypeptides

The inventions introduce novel Cas nuclease inhibiting polypeptides with synthetic/ non-natural amino acids as well as techniques to conjugate it to an antibody or PEG for easy delivery to targeted cells. Bacterial cells respond to phage attack by activating CRISPR-Cas nuclease to digest phage genome; to escape it, phages encode anti-CRIPSR-Cas proteins. Broad-spectrum Cas enzyme inhibitors will allow for better post-translational regulation of CRISPR-Cas system for gene editing. These polypeptides were hitherto unknown and their use along with CRISPR-Cas system for genetic manipulation will improve its efficacy and potential for translation to human applications.



  • Anti-CRISPR polypeptides are the tools which will efficiently target the genes being edited
  • Large number of clinical trials are currently using CRISPR-Cas systems to treat diseases- from hematological malignancies to treating HIV via permanent genetic modifications.  However, a major risk involved in using CRISPR-Cas based gene therapy are off-target effects, which may lead to permanent changes in patient genome at non-target sites. 
  • Anti-CRISPR polypeptides allow for long-term regulation of CRISPR-Cas therapy without any off-target effects. They can be introduced independently of the CRISPR system, and they will maintain activity over longer durations.
  • Anti-CRISPR polypeptides act with a better specificity are easier to design and synthesize, when compared to small molecule inhibitors.

Contact Information

Name: Catherine Smith


Phone: 510-646-0631