ABSTRACT
Elevated Granzyme B (GzmB) levels are associated with many chronic inflammatory conditions including vascular, autoimmune and skin diseases. As a serine protease that induces apoptosis in tumor cells, GzmB is an essential part of the immune system. However, high levels of GzmB also result in the random cleavage of extracellular matrix (ECM) proteins, which leads to damaged tissue structure and elasticity. Our project aim is to prevent tissue damage from chronic inflammation by limiting GzmB activity in the ECM without affecting its intracellular functions. We mutated an extracellular protein (ACT) to allow it to bind and inhibit GzmB specifically in the ECM. To deliver this GzmB inhibitor into inflamed sites without bacteria entering the body, we envision two different prototypes: a bandage with a semi-permeable membrane to target localized sites, and a cream containing only the desired protein for general topical use.