Development of cell-free protein synthesis platforms for discovery and/or production of biologicals

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Expected Outcome: This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Maintaining an innovative, sustainable, and competitive EU health industry”. To that end, proposals under this topic should aim to deliver results that are directed at, tailored towards and contributing to all the following expected outcomes: Biopharmaceutical industries get access to streamlined development and production processes for peptide- or protein-based biologicals. Health systems benefit from the availability of enhanced or decentralised production systems for innovative health technologies that involve peptides or proteins, and which improve health and care. Citizens and patients will benefit from better access, availability and affordability of pharmaceuticals based on biologicals. Scope: Cell-Free Protein Synthesis (CFPS) has been employed in fundamental biological research for decades, however, interest for the approach as a viable means for drug development and production has only emerged in recent years. The advantages that CFPS provides in terms of efficiency, simplicity, flexibility, cost- and time savings outweigh the hurdles that are still to be overcome for CFPS to become a routine manufacturing system for peptide- or protein-based biologicals. Currently, there are several CFPS systems used that are either based on prokaryotic or eukaryotic cell lysates (including mammalian) or fully synthetic systems consisting of all the molecular machinery necessary to create functional proteins. The choice of a specific lysate is dictated by the target protein and the end-use application. Proteins that require post-translational modification are generally produced using lysates of mammalian cells. Hence systems based on mammalian cells are of particular interest as they combine properties inherent to eukaryotic cells and their ability to produce human-like glycosylated proteins with the advantages of cell-free synthesis. These proteins include antibody fragments, antigens, virus-like particles, cytokines, enzymes, antimicrobial peptides and proteins containing non-natural amino acids. The benefits of CFPS are manifold, from ease of handling and scalability, on-demand launch of production, ability to rapidly switch products, simplified purification to facilitated standardisation and quality control. CFPS needs less energy resources, the manufacturing footprint is less complex and smaller than in cell cultivation and it enables production of proteins that have toxic effects on cells. In addition, CFPS has the potential as an enabling technology for personalised medicines and is amenable to decentralised manufacturing. CFPS has gained even more interest in the recent past owing to advances in synthetic biology and thanks to the rise of Machine-Learning/Artificial Intelligence (ML/AI). The use of generative deep learning and artificial intelligence has high potential in the de-novo design of…