Combinatorial protein design platform for safe, high-potency CRISPR activators
This technology is a combinatorial protein design platform that rapidly generates and screens engineered protein variants to produce safer, more potent CRISPR gene activators for research, biotechnology, and therapeutic applications.
Unmet Need: Scalable platform for low-toxicity, high-performance CRISPR activators
Current CRISPR gene activation systems can exhibit inconsistent effectiveness across different genes and cell types, unintended activation of non-target genes, and cellular toxicity, limiting safe use. Efforts to improve these tools are hindered by slow, low-throughput development methods that make it difficult to systematically optimize performance while minimizing harmful effects. These challenges reduce research reliability and pose barriers to clinical translation.
The Technology: Rapid barcoded screening of engineered CRISPR activator variants
The technology uses a combinatorial protein engineering approach to generate large libraries of engineered protein variants by assembling different functional domains into new configurations, each labeled with a unique barcode that enables simultaneous pooled testing of thousands of designs in cells. Gene activation performance and cellular fitness are measured in parallel, allowing potent variants to be identified while toxic designs are naturally depleted. Because full-length domains or entire proteins can be combined, the platform can explore a wide range of designs directly in living cells.
This technology was validated by the identification of two engineered CRISPR activators (MHV and MMH) that demonstrate strong gene activation across multiple targets and cell types while exhibiting lower cellular toxicity than commonly used activators.
Applications:
- Potent, low-toxicity CRISPR activators for robust gene activation across targets and cell types
- Platform for large-scale discovery and optimization of engineered protein variants
- Engineering of immune cells and stem cells for therapeutic applications
- Synthetic biology and programmable genetic circuit development
- Clinical gene therapy
Advantages:
- High-throughput generation and screening of protein variants
- Faster discovery
- Generalizable to diverse proteins and applications
- Lower cellular toxicity
- Strong, consistent gene activation across targets and cell types
Lead Inventor:
Patent Information:
Patent Pending
Related Publications:
Tech Ventures Reference:
IR CU24283
Licensing Contact: Cynthia Lang