Abstract
SummaryOver the past two decades, the moss Physcomitrella patens has been developed from scratch to a model species in basic research and in biotechnology. A fully sequenced genome, outstanding possibilities for precise genome‐engineering via homologous recombination (knockout moss), a certified GMP production in moss bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein glycosylation, remarkable batch‐to‐batch stability and a safe cryopreservation for master cell banking are some of the key features of the moss system. Several human proteins are being produced in this system as potential biopharmaceuticals. Among the products are tumour‐directed monoclonal antibodies with enhanced antibody‐dependent cytotoxicity (ADCC), vascular endothelial growth factor (VEGF), complement factor H (FH), keratinocyte growth factor (FGF7/KGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), asialo‐erythropoietin (asialo‐EPO, AEPO), alpha‐galactosidase (aGal) and beta‐glucocerebrosidase (GBA). Further, an Env‐derived multi‐epitope HIV protein as a candidate vaccine was produced, and first steps for a metabolic engineering of P. patens have been made. Some of the recombinant biopharmaceuticals from moss bioreactors are not only similar to those produced in mammalian systems such as CHO cells, but are of superior quality (biobetters). The first moss‐made pharmaceutical, aGal to treat Morbus Fabry, is in clinical trials.
Highlights
Most recombinant biopharmaceuticals are complex human glycoproteins
The benchmarks for any production system are mammalian cell factories, especially CHO cells, which were derived from Chinese hamster ovaries (Beck et al, 2008; Durocher and Butler, 2009)
In comparison with the benchmarks, three major challenges remain before plants can be widely used as alternative cell factories: 1. The amounts of recombinant products need to be enhanced by several techniques
Summary
Over the past two decades, the moss Physcomitrella patens has been developed from scratch to a model species in basic research and in biotechnology. A fully sequenced genome, outstanding possibilities for precise genome-engineering via homologous recombination (knockout moss), a certified GMP production in moss bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein glycosylation, remarkable batch-to-batch stability and a safe cryopreservation for master cell banking are some of the key features of the moss system. Several human proteins are being produced in this system as potential biopharmaceuticals. An Env-derived multi-epitope HIV protein as a candidate vaccine was produced, and first steps for a metabolic engineering of P. patens have been made. Some of the recombinant biopharmaceuticals from moss bioreactors are similar to those produced in mammalian systems such as CHO cells, but are of superior quality (biobetters). The first moss-made pharmaceutical, aGal to treat Morbus Fabry, is in clinical trials
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