10090307The RNA desktop biofoundry: end to end platform for RNA R&D, process development and manufacturingClosedCollaborative R&DInnovate UKA major focus of synthetic biology has been on programmable genetic regulatory systems to control gene expression. However, in the past years the attention has turned to RNA regulators as well for this task because of their versatility and the emergence of powerful new RNA design principles. The use of RNA regulators has been proven effective in numerous applications beneficial to human health such as (1) replacement therapy, where mRNA is administered to the patient to compensate for a defective gene/protein, or to supply therapeutic proteins; (2) vaccination, where mRNA encoding specific antigen(s) is administered to elicit protective immunity; (3) cell therapy, where mRNA is transfected into the cells ex vivo to alter cell phenotype or function, and then these cells are delivered into the patient. While we see increased global investments to scale existing RNA manufacturing capabilities due to the success of mRNA vaccines, such investments alone will not be enough to accelerate innovation, development and adoption of RNA-biomedicines into the market at the pace needed. The discovery, development and manufacturing of RNA-based biomedicines is subject to the same limitations as the development of other biologics: the route from R&D and process development to manufacturing is highly inefficient due to the differences in the technologies used at each stage and the need for centralized specialized facilities and personnel for manufacturing. In order to accelerate and democratize RNA-based biomedicine development there is a significant need for affordable R&D tools that allow a seamless transition to manufacturing. In particular, there is a demand for tools that can improve yields, improve delivery, automate robust protocols and enable predictive scaling from R&D scale to population scale. This project will develop a small-scale fully automated RNA biofoundry and demonstrate the productivity, democratization and efficiency to translate the process to a scalable manufacturing set up. To achieve this outcome, BiologIC will leverage the current IVT (InnovateUK10025959), microbioreactor modules of the BiologIC platform, build RNA delivery modules and interconnect all the modules using BiologIC's patented architecture design. Innovations include: -Automated end-to-end biofoundry integrating RNA synthesis, encapsulation and testing -Modular mRNA system integrated with a modular cell growth microbioreactor in a single system -Integrated electroporation module for RNA delivery into the cells (delivery type-I) -Integrated microfluidic chip for RNA encapsulation into LNPs for RNA delivery into the cells (delivery type-II) -Integrated mixing module for RNA/cationic polymer complex formation for delivery into the cells (delivery type-III)