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H6-trC1INH(MGS)-MSA
- Development stage
- Preclinical
- Lead developer
- McMaster University
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes
- Administration
- Intravenous
01
Overview
H6-trC1INH(MGS)-MSA is a recombinant fusion protein designed for the prophylactic treatment of Hereditary Angioedema (HAE). It consists of a hexahistidine-tagged, truncated human C1-esterase inhibitor (C1INH) lacking the first 97 N-terminal residues, with three mutated N-linked glycosylation sites (N216Q, N231Q, and N330Q), fused to murine serum albumin (MSA) via a (Gly4Ser)3 linker. The truncation and glycosylation mutations simplify the protein for expression in *Pichia pastoris*, while the albumin fusion significantly extends the circulatory half-life (approximately 3-fold compared to the unfused variant) by avoiding renal filtration and utilizing FcRn-mediated recycling. The molecule retains the ability to inhibit its primary targets, plasma kallikrein (Pka) and C1s, which are critical in the regulation of the contact and complement systems to prevent excessive bradykinin generation.
- Other names
- hexahistidine-tagged truncated C1INH(MGS)-murine serum albumin fusion protein
02
Targets
C1S (Complement component 1s subcomponent serine protease)KLKB1 (Plasma kallikrein)
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