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

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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.