Predictive REagent-Antibody Replacement Technology stage 2 - Translation (PRe-ART 2T)

PRe-ART- 2t将把FET-OPEN项目PRe-ART（预测性试剂抗体替代技术）从实验室概念验证转化为投资准备。我们保留了PRe-ART的最初目标，即颠覆试剂抗体市场，该市场在四十多年后仍然基于单克隆抗体（mab）来检测生物分子，而50%的商业试剂mab已被证明不能正常工作。PRe-ART已经成功地为TRL3提供了基础平台技术。PRe-ART-2T将把这项技术发展到TRL6，从而使我们的目标能够颠覆试剂抗体市场，用高性能的合成替代品取代低质量的商业动物源性试剂单克隆抗体，这些替代品是通过结合我们的实验预先选择的氨基酸结合基元百科全书中的模块创建的。多学科是目前PRe-ART实验成功的关键。通过结合生物化学，计算蛋白质设计和蛋白质工程方面的集体专业知识，我们创造了一个良性循环，其中生化和结构数据（UZH）为我们的新型计算诱变预测（UBT）提供信息，为高度指定的基因文库（Aston）的合成提供信息，其蛋白质产物通过新型高通量筛选（UZH）进行分析。关键命中被分析生化和结构（UZH）和结果数据通知下一个周期。随着循环的重复，更大的特异性随之而来。因此，我们已经创造了许多新的和非常稳定的氨基酸结合基序，我们也以模块化的方式成功地结合了预测的肽目标。该项目还产生了新的建模（ATLIGATOR）、诱变（ParaMAX随机化）和筛选程序。在PRe-ART-T2中，我们将完成天然和修饰氨基酸的dArmRPs套件，并通过为四个商业相关目标创建原型进一步研究它们的模块化。在PRe-ART-2T结束时，我们预计将寻求约2000万欧元的投资。

PRe-ART-2T will translate FET-OPEN project PRe-ART (Predictive Reagent Antibody Replacement Technology) from laboratory proof of-concept to investment readiness. We retain PRe-ART’s original aim to disrupt the reagent antibody market, which after forty years plus, is still based on monoclonal antibodies (mAbs) to detect biomolecules, when 50% of all commercial reagent mAbs have been shown to not function correctly. PRe-ART has successfully delivered a foundational platform technology to TRL3. PRe-ART-2T will develop the technology to TRL6, so empowering our aim to disrupt the reagent antibody market by replacing low-quality, commercial animal-derived reagent mAbs with high-performing synthetic alternatives, created by combining modules from our encyclopaedia of experimentally pre-selected amino acid-binding motifs. Multidisciplinary is key to the current experimental success of PRe-ART. By combining collective expertise in biochemistry, computational protein design and protein engineering, we have created a virtuous circle wherein biochemical & structural data (UZH) inform our novel computational mutagenic predictions (UBT), that inform synthesis of highly specified gene libraries (Aston), whose protein products are analysed though novel high-throughput screens (UZH). Key hits are analysed biochemically and structurally (UZH) and resulting data inform the next cycle. As the cycle reiterates, greater specificity ensues. We have thus created many new and extremely stable amino acid-binding motifs that we have also combined in a modular manner to successfully bind predicted peptide targets. The project has also resulted in novel modelling (ATLIGATOR), mutagenic (ParaMAX randomization) and screening procedures. In PRe-ART-T2 we will complete our suite of dArmRPs for natural and modified amino acids and further study their modularity by creating prototypes for four commercially relevant targets. At the end of the PRe-ART-2T, we expect to seek investment of ~€20 M.