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H6-trC1INH(MGS) is a recombinant, truncated, and non-glycosylated variant of the human C1 esterase inhibitor (C1INH), designed for the treatment and prophylaxis of Hereditary Angioedema (HAE). This construct lacks the first 97 amino acids of the native N-terminal domain and features three mutated N-linked glycosylation sites (N216Q, N231Q, and N330Q) within the serpin domain to simplify the protein structure and facilitate expression in eukaryotic systems like *Pichia pastoris*. It includes an N-terminal hexahistidine tag for purification. Functionally, H6-trC1INH(MGS) acts as a serine protease inhibitor (serpin), targeting plasma kallikrein (Pka) and the C1s subcomponent of the complement system to regulate vascular permeability and inflammation. Due to its reduced molecular weight (~43 kDa) and lack of glycosylation, it has a short circulatory half-life, serving as a base molecule for half-life extension strategies such as fusion to serum albumin.
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