Moss-Produced, Glycosylation-Optimized Human Factor H for Therapeutic Application in Complement Disorders

Area of Science:

• Biochemistry
• Immunology
• Biotechnology

Background:

• Genetic defects in complement regulatory proteins, particularly factor H, cause severe renal diseases and age-related macular degeneration.
• Current therapeutic options for these complement-mediated disorders are limited, highlighting the need for novel treatments targeting the alternative pathway.
• Recombinant factor H is not commercially available, creating a gap in potential therapeutic strategies.

Purpose of the Study:

• To produce an improved, glycosylation-optimized recombinant human factor H in moss (Physcomitrella patens).
• To assess the therapeutic potential of this moss-derived factor H for complement dysregulation disorders.

Main Methods:

• Expression of full-length recombinant human factor H in Physcomitrella patens.
• Purification of the recombinant factor H, removing plant-specific glycan residues.
• In vitro testing of complement regulatory activity and blockade of alternative pathway activation.
• In vivo assessment in a murine model of C3 glomerulopathy.

Main Results:

• Production of approximately 1 mg/L of purified, glycosylation-optimized recombinant human factor H.
• Demonstrated full in vitro complement regulatory activity comparable to plasma-derived factor H.
• Efficiently blocked lipopolysaccharide-induced alternative pathway activation and patient serum-induced hemolysis.
• Reduced C3 deposition and increased serum C3 levels in a murine model of C3 glomerulopathy.

Conclusions:

• Moss-produced recombinant human factor H is a promising therapeutic candidate for diseases involving complement dysregulation.
• The improved glycosylation profile enhances its suitability for therapeutic intervention.
• This approach offers a potential solution for the lack of commercially available therapeutic factor H.