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. 2022 Dec 6;23(23):15440. doi: 10.3390/ijms232315440

Figure 14.

Figure 14

Concepts of degrader technologies hijacking lysosomal pathway. (a) LYTACs utilize a glycan tag to mark an extracellular POI for intracellular lysosomal degradation following shuttling receptor-mediated internalization. (b) Mechanism of action of MoDE-A bifunctional molecules. MoDE-A brings the target protein to ASGPR on hepatocytes for lysosomal degradation. (c) Bispecific aptamer chimeras use DNA aptamers to target CI-M6PR and transmembrane POI. (d) AbTAC recruits RNF43 to internalize cell surface proteins. (e) GlueTAC consists of a single-domain antibody, a cell-penetrating peptide and a lysosome-sorting sequence. The single-domain antibody is responsible for targeting POI and CPP-induced endocytosis of the complex followed by lysosomal degradation. ASGPR: asialoglycoprotein receptor; CI-M6PR: cation-independent mannose-6-phosphonate receptor; CPP-LSS: cell-penetrating peptide and lysosome-sorting sequence; LTR: lysosomal targeted receptor; POI: protein of interest; RNF43: RING finger protein 43.