10172401Engineering next-generation proteins to unlock a derisked anti-fibrotic therapyClosedFast Start ResponseInnovate UKFibrosis is a major global health burden responsible for ~18% of all global deaths. It underlies many different chronic illnesses such as liver cirrhosis, heart failure, interstitial lung disease, and chronic kidney disease. These conditions involve the progressive scarring of tissues, which eventually leads to organ failure. Current treatments are extremely limited and can only modestly slow down the disease in a small number of patients. There is a clear and urgent need for new therapies that are both effective and durable in a much larger number of patients living with fibrotic diseases. This project applies synthetic biology and protein engineering to develop novel protein therapeutics with improved drug-like properties. The focus is on optimising a natural human protein that has shown promise in early studies of fibrotic disease. Although it has therapeutic potential, the native form of the protein suffers from short half-life, instability, and poor pharmacokinetics, which have historically limited its utility. Using a combination of engineering approaches and rational design, we aim to systematically re-engineer the protein to improve stability, manufacturability, and _in vivo_ performance. The project will generate and screen a panel of engineered protein variants, with the goal of identifying candidates that meet pre-defined criteria for biophysical stability and therapeutic potential. These leads will be prioritised for further testing and future development. By applying tools and principles from synthetic biology, this work demonstrates how engineering biology can unlock enhanced therapeutic functionality in naturally occurring proteins, transforming them into practical drug candidates. This feasibility-stage project represents a step toward a new therapeutic modality for fibrosis, with potential applications across multiple diseases. It also highlights the broader promise of synthetic biology in developing next-generation biologics for unmet medical needs.