Sialic acids are the negatively charged, terminal monosaccharides of carbohydrate chains that are attached to glycoproteins and glycolipids (glycans).

CMP-sialic acid acts as a sialic acid donor to sialylate glycans on nascent glycoproteins and glycolipids in the Golgi apparatus; it also acts as a cytoplasmic feedback inhibitor of the UDP-GlcNAc 2-epimerase enzyme by binding to its allosteric site.

There is normally some level of glycan sialylation within a glycoprotein, but with the observation that incomplete sialylation can lead to reduced therapeutic activity, it becomes relevant to assess the cell-lines and culture media to “humanise” the glycoprotein to improve performance and yield and reduce manufacturing costs.

The activity of the GNE enzyme is now recognised as one of the defining features in the efficient production of sialylated recombinant glycoprotein therapeutic drugs.

The therapeutic potential for ManNAc is currently being assessed in several diseases in which therapy could benefit from its ability to enhance the biosynthesis of sialic acid.

GNE myopathy is a rare genetic disorder caused by hyposialylated muscle proteins and glycosphingolipids[10] because there is insufficient metabolic ManNAc to form the Neu5Ac terminal sugar.