Bringing enzymes to the proximity party.

Enzymes are used to treat a wide variety of human diseases, including lysosomal storage disorders, clotting disorders, and cancers. While enzyme therapeutics catalyze highly specific reactions, they often suffer from a lack of cellular or tissue selectivity. Targeting an enzyme to specific disease-driving cells and tissues can mitigate off-target toxicities and provide novel therapeutic avenues to treat otherwise intractable diseases. Targeted enzymes have been used to treat cancer, in which the enzyme is either carefully selected or engineered to reduce on-target off-tumor toxicity, or to treat lysosomal storage disorders in cell types that are not addressed by standard enzyme replacement therapies. In this review, we discuss the different targeted enzyme modalities and comment on the future of these approaches.