10075946UNIVERCell: An engineered red blood cell line to unlock a new, universal therapeutic modalityClosedCollaborative R&DInnovate UKVast research and development spend is funnelled into next generation therapeutics - with gene therapy applications leading the field. Gene therapy is applicable to monogenic diseases but is more difficult to apply to more complex diseases that can arise due to alterations in more than one gene. Recombinant proteins are potentially an ideal modality for these complex cases - for example, metabolic diseases that result in hyperammonemia and hyperoxaluria- but they are incredibly challenging to deploy, having short life-times within the circulatory system. This project will develop an alternative to traditional delivery methods, using red blood cells (RBC). RBCs circulate in the body for about four months and have a much longer half-life as compared to conventional medications. RBCs do not have a nucleus/DNA and hence do not present the risk of uncontrolled cell division/cancer, thereby promising to be safe delivery vehicles for therapeutics. However, the generation of RBCs at commercial levels is not established so far due to the challenges of growing enough RBCs at commercially reasonable cost from donated stem cells. Scarlet Therapeutics aims to pioneer the commercially viable production of eRBC from cell lines and manipulating them to contain therapeutic proteins of interest. In this project, we will upgrade our RBC lines by sourcing cells from more universal blood donors to enable us to create a RBC platform that can be engineered to contain therapeutic proteins of interest and are suitable for use in humans. This would be designed to be applicable to patients of almost all blood types. We estimate that approximately 97% of people will be covered if we use O negative blood and 10 different blood type variations of the main important major and major blood groups. In the first instance (immediately post-project) we will deploy our engineered RBCs for the treatment of metabolic disorders. In the longer term (5 years post-project), our project output also provides the foundation for opportunities for meeting the high demand for blood transfusion, especially for rare blood types or those patients who require regular transfusions throughout life due to thalassemia or sickle cell disease (approx. 420 million people worldwide).