In Situ Glycan Analysis and Editing in Living Systems

Abstract

Besides proteins and nucleic acids, carbohydrates are also ubiquitous building blocks of living systems. Approximately 70% of mammalian proteins are glycosylated. Glycans not only provide structural support for living systems but also act as crucial regulators of cellular functions. As a result, they are considered essential pieces of the life science puzzle. However, research on glycans has lagged far behind that on proteins and nucleic acids. The main reason is that glycans are not direct products of gene coding, and their synthesis is nontemplated. In addition, the diversity of monosaccharide species and their linkage patterns contribute to the complexity of the glycan structures, which is the molecular basis for their diverse functions. Research in glycobiology is extremely challenging, especially for the in situ elucidation of glycan structures and functions. There is an urgent need to develop highly specific glycan labeling tools and imaging methods and devise glycan editing strategies. This Perspective focuses on the challenges of in situ analysis of glycans in living systems at three spatial levels (i.e., cell, tissue, and in vivo) and highlights recent advances and directions in glycan labeling, imaging, and editing tools. We believe that examining the current development landscape and the existing bottlenecks can drive the evolution of in situ glycan analysis and intervention strategies and provide glycan-based insights for clinical diagnosis and therapeutics.

Functional Interface for Glycoprotein Sensing: Focusing on Biosensors

“…Another more promising future development should be directed to the precise discrimination of specific different glycoforms on glycoproteins and the in situ cell surface glycan sensing, labeling or imaging, which have been attracting much research interests. ,, Glycans on the cell surface would change with the progress of diseases, and aberrant glycosylation is often related to tumor development, so intricate glycosylation patterns are gradually becoming new biomarkers for early diagnosis of various diseases.…”