Application
This technology enables targeted chemical correction of missense mutations in proteins using a modular heterotrifunctional molecule platform.
Key Benefits
- Restores protein function by chemically mimicking healthy amino acid side chains.
- Modular toolkit allows rapid customization for diverse protein targets.
- Validated across multiple biochemical and cellular assays.
Market Summary
Missense mutations are a leading cause of many serious diseases, including cancer, cardiovascular and neurodegenerative disorders, and inherited conditions. These mutations often result in dysfunctional proteins, for which few corrective therapies exist. Current approaches focus on symptom management or gene-level interventions, which can be complex and imprecise. There is a significant unmet need for targeted, protein-level solutions that can restore native function without altering the genome.
Technical Summary
The invention features a heterotrifunctional molecule designed to repair mutated proteins by selectively binding to the defective amino acid, chemically modifying it, and restoring its native interactions using a prosthetic group. The molecule includes a selective ligand, a reactive chemical moiety, and a side-chain mimic, all connected by optimized linkers. A complementary chemical toolkit enables rapid assembly and customization of these molecules using modular building blocks and click chemistry. Validation includes TR-FRET, GST-pulldown, BRET, NanoPCA, co-IP, BLI, RNA-seq, qPCR, and cell viability assays, demonstrating restored protein function in both lab and patient-derived cells.
Development Stage
Validated in vitro and in cell-based assays; toolkit available for research use.
