Current achievements in the production of complex biopharmaceuticals with moss bioreactors.

Transgenic plants are promising alternatives for the low-cost and safe pathogen-free production of complex recombinant pharmaceutical proteins (molecular farming). Plants as higher eukaryotes perform posttranslational modifications similar to those of mammalian cells. However, plant-specific protein N-glycosylation was shown to be immunogenic, a fact that represents a drawback for many plant systems in biopharmaceutical production. The moss Physcomitrella patens offers unique properties as a contained system for protein production. It is grown in the predominant haploid gametophytic stage as tissue suspension cultures in photobioreactors. Efficient secretory signals and a transient transfection system allow the secretion of freshly synthesized proteins to the surrounding medium. The key advantage of Physcomitrella compared to other plant systems is the feasibility of targeted gene replacements. By this means, moss strains with non-immunogenic humanized glycan patterns were created. Here we present an overview of the relevant aspects for establishing moss as a production system for recombinant biopharmaceuticals.