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Moss?¢????made pharmaceuticals: from bench to bedside

机译:苔藓制成的药品:从长凳到床头

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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. 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.
机译:在过去的二十年中,基础研究和生物技术中的藓类Physcomitrella patens已从零开始发展成为典型物种。全序列化的基因组,通过同源重组(敲除苔藓)进行工程改造,在苔藓生物反应器中通过GMP认证生产的产品,成功升级到500升L波反应器,蛋白质糖基化的出色同质性moss系统的一些关键特性是,批处理的稳定性和对主细胞库的安全冷冻保存是非常重要的。该系统中正在生产几种人类蛋白质,作为潜在的生物药物。这些产品包括具有增强的抗体依赖性细胞毒性(ADCC),血管内皮生长因子(VEGF),补体因子H(FH),角质形成细胞生长因子(FGF7 / KGF),表皮生长因子(EGF),肝细胞生长因子(HGF),脱唾液酸促红细胞生成素(asialo ??????? EPO,AEPO),α???????半乳糖苷酶(aGal)和β-葡糖脑苷脂酶(GBA)。此外,产生了由Env来源的多种表位HIV蛋白作为候选疫苗,并且已经进行了对P.β型小鼠进行代谢工程化的第一步。来自苔藓生物反应器的一些重组生物药物不仅与哺乳动物系统(例如CHO细胞)中产生的重组生物药物相似,而且质量高(生物素)。第一种由苔藓制成的药物aGal用于治疗Morbus Fabry,目前正在临床试验中。

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