Abstract
Cold storage at 4 °C enhances platelet hemostatic function but induces a well-characterized storage lesion, including glycoprotein Ib (GPIb) clustering, desialylation, premature activation, and apoptosis. These alterations result in rapid clearance of transfused platelets, limiting their clinical utility despite improved function. Tardigrade-derived intrinsically disordered proteins (IDPs), such as CAHS, MAHS, and RAHS, form protective amorphous glass-like matrices under stress conditions, stabilizing proteins and membranes. This project aims to harness these properties to mitigate cold-induced platelet damage by engineering megakaryocytes and platelets to express IDPs. By incorporating optimized IDP gene constructs (synthesized via TWIST Bioscience), we seek to create platelets with enhanced structural resilience during cold storage, preserving both function and circulation time.