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Bacterial Exosomes Expand the Oligosaccharide Targeting Ligand Space Beyond GalNAc

N-acetylgalactosamine (GalNAc) is the prototypical RNA therapeutic targeting ligand, that delivered clinical and commercial value by enhancing hepatocyte drug loading by ~60x across RNA drug classes. Exploring the oligosaccharide chemical space for alternatives that target other specific cell types of therapeutic interest is restricted by commercial availability, chemical synthesis complexity, and limited biocatalyst enzyme availability. Bacterial exosomes (outer membrane vesicles) can help produce membrane-embedded glycosyltransferases that retain substrate affinity, opening up new options in biofabrication and exosome targeting for biotherapeutics.