Development of second-generation S. cerevisiae hosts for enhanced protein yield and quality

开发第二代酿酒酵母宿主以提高蛋白质产量和质量

• 批准号: 105734
• 金额: $ 38.9万
• 依托单位: PHENOTYPECA LIMITED
• 依托单位国家: 英国
• 项目类别: Study
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=105734
• 关键词: Development; second; generation; S.; cerevisiae

Recombinant protein expression is the keystone manufacturing technique supporting production of many biological therapies. A large number of protein expression systems exist, but the majority of biological drugs and protein products that are approved for clinical use have been manufactured using mammalian cell culture techniques. These manufacturing processes are laborious, slow, and expensive.Yeast systems offer a significantly simpler way of expressing recombinant proteins at scale compared to mammalian cell culture, and at a greatly reduced cost.A number of yeast protein expression systems have been commercialised. However, the baker's yeast (Saccharomyces cerevisiae) expression systems, which are most commonly used in industry for biologics production, have never themselves been widely commercialised by the companies that developed them. The patent protection for these baker's yeast systems has now expired or is expiring. This engenders considerable freedom to create new systems and develop new IP surrounding enhanced, second-generation protein expression systems utilising S. cerevisiae as their protein-production powerhouse and making this technology widely available to new companies wishing to bring recombinant products to the market.The project will enable Phenotypeca to develop novel strains of S. cerevisiae to be created that can be quickly and easily tailored to optimize production of recombinant proteins.In this instance, the platform will be exemplified by producing a protein (H-Guard) for another UK SME - Invizius - which is a coating used on dialysis equipment to prevent inflammatory responses induced by repeated exposure to dialyser membranes.Invizius will work alongside the Centre for Process Innovation (CPI), who join the consortium as grant funded partners to conduct industrial fermentation modelling to identify the most suitable for scale-up production.The project supports Phenotypeca to become a service provider for clients wanting S. cerevisiae-based protein expression systems. There are currently no commercial providers of industrial S. cerevisiae systems -- all S. cerevisiae systems used industrially are proprietary systems developed in-house by other companies who don't want to share their technology of offer a development service. Phenotypeca is attempting to overcome the unmet market need for S. cerevisiae protein expression systems, especially for a class of therapeutic peptides for which Pichia pastoris-based yeast systems cannot meet the quality and regulatory requirements.

重组蛋白表达是支持许多生物疗法生产的关键生产技术。存在大量的蛋白质表达系统，但是大多数被批准用于临床使用的生物药物和蛋白质产品已经使用哺乳动物细胞培养技术制造。这些生产过程费力、缓慢且昂贵。与哺乳动物细胞培养相比，酵母系统提供了一种明显更简单的大规模表达重组蛋白的方法，并且成本大大降低。许多酵母蛋白表达系统已经商业化。然而，面包酵母（酿酒酵母）表达系统，这是最常用的工业生物制剂生产，从来没有被开发它们的公司广泛商业化。这些面包酵母系统的专利保护现在已经到期或即将到期。这产生了相当大的自由，创造新的系统和开发新的IP周围增强，第二代蛋白质表达系统利用S。该项目将使Phenotypeca能够开发新的S.在这种情况下，该平台将通过为另一家英国SME - Invizius生产蛋白质（H-Guard）来举例说明，该蛋白质是一种用于透析设备的涂层，用于防止反复暴露于透析器膜引起的炎症反应。Invizius将与过程创新中心（CPI）合作，他们作为赠款资助的合作伙伴加入该财团，进行工业发酵建模，以确定最适合扩大生产的菌株。该项目支持Phenotypeca成为希望获得S.蛋白质表达系统。目前还没有工业S的商业供应商。酿酒酵母系统-所有S.工业上使用的酿酒系统是由其他公司内部开发的专有系统，这些公司不想分享他们的技术或提供开发服务。Phenotypeca正试图克服S.酿酒酵母蛋白表达系统，特别是对于一类基于巴斯德毕赤酵母的酵母系统不能满足质量和监管要求的治疗肽。