GTC Biotherapeutics (fka GTCB)

[Pre_Clinical]

Lack of glycosylation can promote faster renal clearance, depending on the molecular weight of the protein. For AAT and Factor VII, their molecular weights fall into the range that makes me worry. In addition to my half-life concerns, some aglycosylated proteins (proteins that are normally glycosylated but manufactured in a non-glycosylated form) sometimes have a tendency to be more labile to proteolysis, aggregation, and immunogenicity. In addition, the exact chemical composition of the carbohydrates is tremendously important here, which I'm sure is going to be highly variable as well.