Factor H, a key component of the immune system that is missing in patients suffering from atypical hemolytic uremic syndrome (aHUS) was effectively produced in the moss Physcomitrella patens. In collaboration with the University of Freiburg, Greenovation now aims to humanize the protein to suit it for clinical use.

The complement system is part of the innate immune system, with the mission to eliminate pathogens from an organism. In healthy people, the system helps recognize foreign compounds without enabling the long-winded formation of antibodies.

However, when not regulated strictly, the cell lysis provoking system can turn on endogenous cells. This happens to patients with atypical hemolytic uremic syndrome (aHUS), an extremely rare, chronic disease that leads to kidney failure.

In approximately 10 to 30% of cases, aHUS is caused by the mutation of the recombinant factor H, a negative regulator of the complement system that helps prevent autoimmune attacks.

Nowadays, the disease is treated with plasma donation, kidney transplantation and, since 2011, with eculizumab, a monoclonal antibody that serves as an inhibitor of the complement system. The only downside to this treatment is that the antibody is one of the most expensive drug on Earth…

Greenovation, which has developed a unique technology to produce biopharmaceuticals from moss, wants to establish a new treatment in collaboration with the University of Freiburg. For five years now, the group of Eva Decker succeeded to produce the recombinant factor H in transgenic moss Physcomitrella patens. The model organisms have very promising features. Moss cultures neither contain animal-derived components or pathogens that could affect humans, nor antibiotics that may cause resistance. Furthermore, products stemming from moss have a superior purity.

The challenge now is to humanize the protein. This is no walk in the park as plants use different carbohydrates for glycosylation than humans. Glycotransferases are therefore silenced in Physcomitrella and human enzymes are introduced in the plant. Earlier in March this year, Greenovation and the University of Freiburg started a 2 year project, evaluating the biological efficacy of recombinant factor H in preclinical mice studies.

Should the results come back positive, transgenic moss could potentially provide a cheap and safe opportunity for the clinical use of factor H.

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