Low immunogenicity of lwcas13a protein mutant and application thereof
By mutating the LwCas13a protein with Q436C, K560D, and K76C mutations, the immunogenicity of the Cas13 protein in large mammals was resolved, achieving stable protein expression and efficient gene editing, and reducing the immune response.
Patent Information
- Application Number
- CN202511269339.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-08
- Publication Date
- 2026-01-16
- Estimated Expiration
- 2045-09-08
AI Technical Summary
Long-term expression of the Cas13 protein in large mammals raises immunogenicity concerns, as it may be recognized as a target of the immune system, leading to instability in immune responses and the regulation of targeted RNA.
We designed low-immunogenic LwCas13a protein mutants and introduced mutations such as Q436C, K560D, and K76C into the wild-type LwCas13a protein to reduce its affinity for bovine MHC-I molecules, thereby maintaining the protein's structural stability and nuclease activity.
It significantly reduced the immunogenicity of LwCas13a protein in cattle, ensuring long-term stable protein expression and the ability to regulate the target RNA, maintaining gene editing efficiency, and reducing the rejection response of the immune system.