- Chaperone-mediated Autophagy Protein Degradation Technology (CHAPTAC) has advantages over small molecule PROTAC technology in degrading proteins of interest and can replace antisense and siRNA technology platforms in many indications with greater specificity and greater temporal precision.
- Broad IP protection for our platform technology
- Reversibly degrades a disease protein via lysosome degradation using a clinically-applicable, membrane-permeable “grabbing” peptide
- Provides an alternative strategy in targeted protein degradation when the proteasome is dysfunctional
- Validated both in vitro and in vivo
- Validated on multiple protein targets in cardiovascular, CNS and cancer indications
Here we present a simple, non-virally mediated, cell membrane–permeant, targeting peptide–based system to rapidly and reversibly knock down an endogenous protein of interest by targeting it for lysosomal degradation. As shown in the figure above, the peptide consists of a cell-penetrating domain that can deliver the peptide across the blood-brain barrier and the plasma membrane of cells; a short target protein-binding domain that specifically binds to a target protein of interest with high affinity; and the chaperone-mediated autophagy (CMA)-targeting motif (CTM) that can direct the peptide-protein complex for lysosomal degradation.
Using this technology, we have designed several effective peptides that can acutely and reversibly degrade proteins of interest. Here is one selected example: PP-006 degrades an oncology target protein and reduces cancer cell viability in mice.