We report a strategy for creating a new class of protein transfection materials composed of a functional protein core chemically modified with a dense shell of oligonucleotides. These materials retain the native structure and catalytic ability of the hydrolytic enzyme beta-galactosidase, which serves as the protein core, despite the functionalization of its surface with 15 DNA strands. The covalent attachment of a shell of oligonudeotides to the surface of beta-galactosidase enhances its cellular uptake of by up to similar to 280-fold and allows for the use of working concentrations as low as 100 pM enzyme. DNA-functionalized beta-galactosidase retains its ability to catalyze the hydrolysis of beta-glycosidic linkages once endocytosed, whereas equal concentrations of protein show little to no intracellular catalytic activity.