The research, published recently in the journal Cell , describes a new strategy that allows for the selective degradation and elimination of specific “disease-causing proteins” with spatial and temporal precision in vivo.
Proteins are important regulators and functional components in the body's biological machinery. Abnormal expression or dysfunction of proteins underlies many human diseases.
Traditional small molecule therapies generally inhibit protein function by occupying the protein's active pocket; however, many disease-related proteins lack a pocket that can be targeted by drugs, making them resistant to traditional therapeutic approaches.
To overcome this limitation, researchers from the Institute of Chemistry, Chinese Academy of Sciences (ICCAS) developed an innovative tool called supramolecular targeting chimeras (SupTACs).
This strategy exploits the cell's own ubiquitin-proteasome system by bringing target proteins closer to the degradation machinery, thereby triggering selective proteasomal degradation.
"Existing targeted protein degradation strategies often lack precise control over when and where they work, limiting their effectiveness in vivo and increasing the risk of off-target effects," explains Wang Ming, a professor at ICCAS and lead author of the study.
Specifically, SupTACs demonstrated stable and efficient protein degradation in various animal models, including nonhuman primates. This research marks an important step toward the clinical translation of targeted protein degradation technology, Wang added.
