Here we establish the targeted degradation of extracellular and membrane-associated proteins using conjugates that bind both a cell-surface lysosome-shuttling receptor and the extracellular domain of a target protein. These initial lysosome-targeting chimaeras, which we term LYTACs, consist of a small ...
The lysosome-targeting chimera (LYTAC) approach has shown promise for the targeted degradation of secreted and membrane proteins via lysosomes. However, there have been challenges in design, development, and targeting. Here, we have designed a genetically engineered transferrin receptor (TfR)-mediated ...
The first lysosome targeting chimeras (LYTACs) targeted extracellular and membrane proteins for degradation by bridging a target protein to an endogenous lysosome targeting receptor, the cation-independent mannose-6-phosphate receptor (CI-M6PR). Here we developed LYTACs that engage the asialo...
ArticleAnti-tumor immunotherapy using engineeredbacterial outer membrane vesicles fused tolysosome-targeting chimeras mediated bytransferrin receptorGraphical abstractHighlightsd A gene-encoded TfR-LYTAC is developed for lysosomaldegradation of extracellular proteinsd TfR-LYTAC is eff i ciently targetedto thetum...
Gag encoded with the translocon, transmembrane and cytoplasmic lysosomal membrane targeting sequences of LAMP, without the luminal domain, was poorly expressed, did not traffic to lysosomes or MHC II compartments of transfected cells, and elicited a limited immune response from DNA immunized mice. In...
West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein: increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enhanced neutralizing antibody response...