Selective editing of N-glycan signals on living cell surface

Glycan signals on living cell surface act as biological codes that enable communication between cells and their external environment. They play pivotal roles in processes such as cell recognition and immune responses. In recent years, glycan editing technologies based on glycosyltransferases and glycosidases have advanced rapidly, enabling the precise and dynamic manipulation of glycosylation modifications on living cell surface in situ. Compared to gene-editing, chemical metabolic labelling and biorthogonal chemistry, based on glycan engineering approach marks a new stage in glycobiology research, with transitional, dose-dependent and controllable editing of specific N-glycan structures/signals. Due to their high compatibilities to cellular states, those enzymes can edit and remodel complex glycan structures in real time while preserving cell viabilities and functions. This significantly enhances the precision and efficiency of glycan decoding. N-Glycans serve as a major target for glycan editing due to their conserved core architecture and stereotypic assembly, which confer both structural predictability and site-specific modifiability. This review mainly focuses on editing of N-glycan signals on living cell surface using glycosyltransferases and glycosidases. Particularly, sialidase-antibody conjugates improve tumor targeting and reduce side effects compared to single-agent approaches, providing a strong basis for precision immune regulation and next-generation cell therapies.