This review delineates emerging technologies for targeted protein degradation that directly involve lysosomes or proteasomes. It explores their unique features, advantages, and limitations, offering perspectives on future therapeutic applications.
Targeting chimeras (TACs), such as PROTACs, LYTACs, AUTACs, and ATTECs, has emerged as a promising strategy for selectively degrading proteins. The linker of the TACs plays a critical role in determining the spatial arrangement, stabilizing the ternary complex, and determining degradation efficiency.
This review proposes the concept of proteolysis-targeting drug delivery system (ProDDS), surveys the recent research in various ProDDSs, summarizes their design principles, and provides an outlook on future opportunities.
We present a DNA-based LYTAC framework that uses DNA self-assembly to control chimera valency and ligand arrangement. Designing 1-, 3-, and 9-valent chimeras showed that higher binding valency improved protein degradation efficiency.
Targeted protein degradation strategies employing proteins as binders for degradation targets.