Directly Engaging 26S Proteasomes for Ubiquitin-Independent Target Degradation

  • Explore how Seoul National university has developed Prote-a-Tac, a targeted protein degradation strategy that directly engages the 26S proteasome, bypassing the need for Ub ligase-mediated polyubiquitination
  • Discuss how Prote-a-Tac is a heterobifunctional chimera combining a proteasome-binding module with a target-specific antibody, enabling selective degradation of overexpressed and endogenous proteins
  • Outline how the platform is highly modular and specific, allowing flexible target switching and demonstrated high specificity validated by quantitative mass spectrometry
  • Discover how the mRNA-based lipid nanoparticle delivery of Prote-a-Tac in cells and mouse xenograft models resulted in effective target degradation and delayed tumor progression