Engineered protein inhibitors for precise targeting of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a family of 23 zinc-dependent proteases involved in extracellular matrix (ECM) remodeling and are implicated in diseases such as cancer, arthritis, and cardiovascular disorders. Broad-spectrum MMP inhibitors (MMPIs) have proven counterproductive due to the protective roles of certain MMPs and their expression in healthy tissues. Recent advances in protein engineering have enabled the development of highly specific protein-based MMPIs that precisely target individual MMPs. These engineered proteins, often derived from antibody fragments or endogenous MMPIs, offer enhanced selectivity, reduced off-target effects, and improved therapeutic efficacy. This review highlights novel strategies for the precise targeting of MMPs using engineered proteins and discusses their potential to transform diagnostics and treatment of MMP-driven diseases.