LYTACs

Lysosomal-Targeting Chimeras (LYTACs) can target extracellular proteins. LYTACs and MoDE-As tether extracellular or membrane-bound POIs to a recycling receptor, which facilitates internalization and subsequent lysosomal degradation. LYTACs utilize the cation-independent mannose-6-phosphate receptor CI-M6PR, a recycling membrane protein that binds POIs labeled with an MP6n tag. GalNAc-LYTACs and MoDE-As utilize a GalNAC tag to recruit the asialoglycoprotein receptor (ASGPR), a liver-specific lysosomal targeting receptor, for tissue-specific degradation.