A Chinese research team has achieved a major advance in the precise regulation of protein degradation in living organisms, opening new avenues for therapeutic strategies against diseases ranging from cancer to neurodegenerative disorders.

The study, published recently in the journal Cell, describes a novel strategy that enables selective degradation and elimination of specific "disease-causing proteins" with both spatial and temporal precision in vivo.

Proteins are essential regulators and functional components of the body's biological machinery. The abnormal expression or dysfunction of protein underlies many human diseases. Traditional small-molecule therapeutics typically inhibit protein function by occupying their active protein pocket; however, many disease-related proteins lack such druggable pockets, rendering them resistant to traditional therapeutic approaches.

To overcome these limitations, researchers from the Institute of Chemistry, Chinese Academy of Sciences (ICCAS), developed an innovative tool named supramolecular targeting chimeras (SupTACs). This strategy hijacks the cell's own ubiquitin-proteasome system by bringing a protein of interest into proximity with degradation machinery, thereby triggering its selective proteasomal degradation.

"Existing targeted protein degradation strategies often lack precise control over when and where they act, limiting their effectiveness in vivo and increasing the risk of off-target effects," explained Wang Ming, a professor at ICCAS and lead author of the study.

Notably, SupTACs demonstrated stable and efficient protein degradation across multiple animal models, including non-human primates. The study marks an important step toward the clinical translation of targeted protein degradation technologies, Wang added.