Glycosylation engineering of the extracellular loop of CD63 on the surface of exosomes to improve the targeting performance of its DDS

A group from Biomolecular Medicine, Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institute, Huddinge Sweden, etc. has reported about cell‐specific targeting of extracellular vesicles (EVs) though engineering of glycan expression on EVs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719568/

Extracellular vesicles are thought to be promising carriers for the delivery of a variety of chemical and biological drugs. In order to improve the targeting performance of EVs, EVs were engineered to display the glycan of interest.
EV producer cells were genetically engineered to co‐express a glycosylation domain (GD) inserted into the large extracellular loop of CD63 and fucosyltransferase VII (FUT7) or IX (FUT9). P19 (19‐mer, derived from PSGL‐1) and CTP (28‐mer, from beta‐chorionic gonadotropin) were selected as potential sLeX peptide carriers (i.e., as the glycosylation domain). The combination of FUT7 and PSGL-1 resulted in the highest expression of sLeX, and also the combination of FUT9 and PSGL‐1 resulted in the highest expression of Lewis X (LeX) but not sLeX.

Through this strategy, surface display of two types of glycan ligands, sLeX and LeX, on EVs was demonstrated, and achieved high specificity towards activated endothelial cells and dendritic cells, respectively.