PhenoDev: A novel Saccharomyces cerevisiae platform for high-yield protein secretion

重组治疗蛋白和许多疫苗的制造成本很高。目前最先进的蛋白表达系统包括：*哺乳动物中国仓鼠卵巢（CHO）和HEK293系统。_限制：_生长缓慢的细胞，昂贵的培养基，高能量负担（例如，提供二氧化碳和加热细胞培养物），一次性技术的高环境负担，不太适合大规模生产。*龙沙的XS - e。coli_系统。_限制：_无法形成二硫键导致错误折叠的蛋白质聚集为不溶性包涵体，不能分泌，需要细胞裂解和进一步加工才能产生功能蛋白。* Validogen的毕赤酵母系统。限制：转化需要毒性的zeomycin；整合质粒阻碍菌株发育；复杂的知识产权/许可问题；糖化赖氨酸残基可导致功能丧失和不必要的免疫原性；甲醇/氧气供气会造成大规模的火灾风险。很少有pichia衍生产品获得FDA或MHRA的批准。Baker's yeast （_Saccharomyces cerevisiae_）在FDA批准的生物制剂中有着长期、安全的记录，通常被认为是安全的（GRAS），例如胰岛素，并且在工业规模条件下具有天然的适应性，同时正确地生产具有生物活性的真核蛋白。尽管如此，目前还没有“开放”的商业表情系统。面包师的酵母系统通常只开发用于内部使用。收益往往不是最优的；开发时间缓慢，品种不容易适应新产品。这是一个优化和商业化下一代s的机会。酿酒酵母蛋白表达平台为更广阔的治疗药物市场。表现型正在发展_S。基于cerevisiae_的平台“PhenoDev”用于高产表达重组蛋白，以解决这一未满足的需求。为了充分发挥市场潜力，PhenoDev必须通过解决这些疗法所需的蛋白酶和蛋白质折叠问题来优化蛋白质分泌。改进后的PhenoDev平台将由另一家英国中小企业Isogenica进行验证，该公司将受益于_E的替代方案。开发和生产他们想要出售的VHH抗体。

Recombinant therapeutic proteins and many vaccines are costly to manufacture. Current state-of-the-art protein expression systems include:* Mammalian Chinese Hamster Ovary (CHO) and HEK293 systems. _Limitations:_ Slow-growing cells, expensive media, high energy burden (e.g., for supplying CO2, and for heating the cell cultures), high environmental burden with disposable technologies, and less amenable to large-volume manufacture.* Lonza's XS _E. coli_ system. _Limitations:_ Inability to form disulphide bonds causes misfolded proteins to aggregate as insoluble inclusion bodies that are not secreted, requiring cell lysis and further processing to generate functional proteins.* Validogen's _Pichia pastoris_ system. _Limitations:_ Transformations require toxic zeomycin; integrated-plasmids hamper strain development; complex IP/licensing issues; glycated lysine residues can cause loss-of-function and unwanted immunogenicity; methanol/oxygen feeds pose a fire risk at scale. Few _Pichia_-derived products have received FDA or MHRA approval.Baker's yeast (_Saccharomyces cerevisiae_) has a long, safe track-record of FDA approve biologics and is generally regarded as safe (GRAS), e.g., insulins, and has natural adaptability industrial-scale conditions whilst correctly producing biologically active eukaryotic proteins. Despite this, no 'open' commercial expression systems are available. Baker's yeast systems are typically developed for in-house use only. Yields are frequently sub-optimal; development times are slow, and strains are not easily adapted to new products.There is an opportunity to optimise and commercialise the next-generation _S. cerevisiae_ protein expression platform for a broader therapeutics market. Phenotypeca are developing the _S. cerevisiae_-based platform 'PhenoDev' for high-yield expression of recombinant proteins to address this unmet need.To realise the full market potential, PhenoDev must be optimised for protein secretion by solving protease and protein folding issues these therapeutics require.The improved PhenoDev platform will be validated by another UK SME, Isogenica, who will benefit from an alternative to _E. coli_ for developing and producing VHH antibodies they want to sell.