Periodic Reporting for period 2 - PRe-ART (Predictive Reagent Antibody Replacement Technology)
Reporting period: 2018-09-01 to 2020-02-29
Today, global spending on protein-binding reagents amounts to an estimated $ 1.6 billion worldwide, of which $ 700 million occur in the US. As only half of all antibodies are validated and functional, $ 800 million and $ 350 million respectively are misspent. We estimate that 50% of these reagents are used in public research institutions and the other 50% by private companies. Europe's pharma and biotech industries and renowned research institutions would enormously benefit from a technology that will increase quality of all detection reagents, and standardize and customize their production. Thus, PRe-ART has the potential to take over leadership in delivering protein-binding reagents for research in Europe, the US and beyond.
First, in the structure determination of the scaffold. Many crystal structures have been determined which confirmed the general strategy of designing a stable scaffold which can be modified. Therefore, the fundamental building blocks exist, and this could be structurally verified.
Second, in the synthesis of new libraries. Using proprietary know-how, new libraries with carefully biased residue statistics were designed, produced, verified, characterized and successfully implemented in the next steps.,
Third, in developing selection technologies. While all three selection technologies, phage display, ribosome display and yeast display were investigated initially, yeast display was found to suit the project needs best. A very important break-through was reached in the first part of this project in that a novel method could be established which directed selection to the affinity of one single amino acid side chain.
Fourth, in computational design. A very important break-through was reached by creating a browsable atlas of related scaffold proteins, thereby accessing a wealth of structural data. This valuable resource can now form the basis of next-generation designs.
The PRe-ART vision is that mAbs for many applications in biological research will be replaced over the course of a decade by these designer molecules, with the potential to completely disrupt the industry selling low-quality commercial animal-derived reagent antibodies, and thus create a major new technology for biological research.
Thus, PRe-ART will ultimately contribute not only to the health and well-being of the EU citizen through improved diagnostic capability, but also to the economy of the EU through the development of myriad detection products, enabled by this foundational platform technology. The interdisciplinary PRe-ART project will achieve this goal by bringing together three leading labs from different fields, two of which are lead by women PIs, whose joint efforts will achieve this breakthrough S&T target. The PRe-ART project thus closely addresses all specific challenges of the call.