Predictive REagent-Antibody Replacement Technology stage 2-Translation

Introduction

PRe-ART-2T will translate the 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 more than forty years, is still based on monoclonal antibodies (mAbs) to detect biomolecules. Notably, 50% of all commercial reagent mAbs have been shown to not function correctly.

Technology Development

Pre-ART has successfully delivered a foundational platform technology to TRL3. PRe-ART-2T will develop the technology to TRL6, empowering our aim to disrupt the reagent antibody market by:

1. Replacing low-quality, commercial animal-derived reagent mAbs.
2. Providing high-performing synthetic alternatives.
3. Creating these alternatives by combining modules from our encyclopaedia of experimentally pre-selected amino acid-binding motifs.

Multidisciplinary Approach

Multidisciplinarity is key to the current experimental success of PRe-ART. By combining collective expertise in:

• Biochemistry
• Computational protein design
• Protein engineering

We have created a virtuous circle wherein biochemical and structural data (UZH) inform our novel computational mutagenic predictions (UBT). These predictions inform the synthesis of highly-specified gene libraries (Aston), whose protein products are analyzed through novel high-throughput screens (UZH).

Iterative Process

Key hits are analyzed biochemically and structurally (UZH), and the 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.

Innovations and Prototypes

The project has also resulted in novel modeling (ATLIGATOR), mutagenic (ParaMAX randomization), 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.

Investment Goals

At the end of PRe-ART-2T, we expect to seek investment of approximately €20 million.