Cancer is the second leading cause of death in the United States. A major challenge in the development of new classes of cancer therapeutics is to attain selectivity and specificity in targeting cells or tissues of interest while minimizing adverse side effects. Inspired by the recent advances in personalized genomics, protein engineering, and clinically approved biomolecule delivery platforms, our lab is developing a novel approach to engineer selectivity in targeting cancer cells with minimal off-target effects. I am using directed evolution to engineer combinations of enzyme/small molecule pairs where the small-molecule prodrug is metabolized to a cytotoxic compound only in the presence of the engineered enzyme. The prodrug will be completely inert in the absence of this enzyme. I am also developing strategies to selectively deliver mRNA corresponding to the evolved enzyme using LNP/antibody-based targeting approaches. The performance of these potential therapeutic models will be evaluated in cell culture assays and animal models.