Predictive REagent-Antibody Replacement Technology stage 2-Translation

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SBFI

Projektnummer

22.00033

Projekttitel

Predictive REagent-Antibody Replacement Technology stage 2-Translation

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Abstract (Englisch)	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 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. Multidisciplinarity 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 randomisation) and screening procedures. In PRe-ART-2T 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 PRe-ART-2T, we expect to seek investment of ~E20 M.

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Abstract
(Englisch)

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 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. Multidisciplinarity 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 randomisation) and screening procedures. In PRe-ART-2T 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 PRe-ART-2T, we expect to seek investment of ~E20 M.