Lung transplants are life-saving procedures that reduce the mortality rate of patients with severe respiratory diseases. However, approximately 90% of lung transplants are rejected due to an aggressive immune response. Current immunosuppressant drugs, like calcineurin inhibitors (CNIs), are the standard for immunosuppression after lung transplantation due to their ability to lower rejection rates and improve long-term graft survival. Yet, they can lead to complications such as infections, increased cancer risk, and impaired tissue repair due to the widespread immune suppression. To address this, we propose a localized immunosuppressive approach using PD-L1 mRNA therapy. 

Our project aims to enhance lung transplant acceptance by directly delivering PD-L1 mRNA to lung tissue, promoting local expression of the PD-L1 protein. PD-L1 binds to PD-1 receptors on the surface of T-cells, inhibiting their activation and reducing the likelihood of immune response-based rejection. Unlike systemic immunosuppressants, this method looks to target immune function directly to the site of the transplant, minimizing unwanted suppression of immune responses on other regions of the body. 

To accomplish this, we will introduce PD-L1 mRNA into the donated lung tissue, where lung cells will transiently express the PD-L1 protein. This will provide a temporary and adjustable immunosuppressive effect as PD-L1 will degrade with time, allowing for controlled management of immunosuppression. Future projects will focus on optimizing mRNA delivery methods for stability, effectiveness, and duration of PD-L1 expression. Through the application of this localized approach, we hope to improve the survival rate of lung transplantations and decrease risks with standard immunosuppressive therapies.