Mucins are large, highly heterogeneous O-glycoproteins that cover all internal surfaces of the body and are major components in body fluids. They serve many functions in our health, including lubrication and protection of all mucosal surfaces, clearance, neutralization, and adhesion of microorganisms and viruses, providing a barrier for direct contact with epithelial cells, and entrapment and direction of our microbiomes.
Mucins primarily consist of tandem repeat (TR) domains densely covered with O-glycans, and these O-glycan domains contain the functional cues for the microbiome and innate immune system. However, obtaining human mucin molecules in reasonable purity with defined glycans has been a fundamental barrier and limitation for studies of mucins and their complex biology.
GlycoDisplay's platform utilizes a glycoengineered isogenic HEK293 cell library to enable the production of recombinant human mucins with defined glycan structures. Our cell-based mucin array allows us to dissect the binding specificities of glycan-binding proteins, such as lectins, antibodies, and microbes. We also offer expression of secreted mucins with distinct O-glycosylation, both transiently and stably.
Human mucins with custom-designed O-glycans
There are 18 distinct human mucins, and these include secreted and cell-membrane attached mucins. GlycoDisplay's recombinant mucins contain around 200 amino acids derived from human mucins (tandem repeat regions) and with 50-100 O-glycans with defined structures.
Our recombinant human mucins have unique benefits compared to isolated animal mucins:
- Distinct human mucins with human type O-glycans
- Homogeneous molecules with tags
- Glycans can be custom-designed to dissect functions
- Mucins can be produced consistently in large scale
HEK 293 wild type cells are predicted to produce a mixture of ST, Disialyl T (DiST) and sialylated core2 O-glycan structures. GlycoDisplay apply gene enginerring technology (gene knock out (KO), knock in (KI), and activation (AC)) to generate O-glycoengineered HEK293 cell library that includes O-glycan structures with DiSialylT (DiST), SialylT (ST), Core1 (T), Tn and STn structure.
Nason R, Bull C, Konstantinidi A, Sun L, Ye Z, Halim A, Du W, Sørensen DM, Durbesson F, Furukawa S, Mandel U, Joshi HJ, Dworkin LA, Hansen L, David L, Iverson TM, Bensing BA, Sullam PM, Varki A, Vries E, Haan C, Vincentelli R, Henrissat B, Vakhrushev S, Clausen H, Narimatsu Y (2021): Display of the human mucinome with defined O-glycans by gene engineered cells. Nat Commun, 1;12(1):4070. DOI: 10.1038/s41467-021-24366-4.