title: DNA-Mediated Cellular Delivery of Functional Enzymes.
abstract: 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 β-galactosidase, which serves as the protein core, despite the functionalization of its surface with ∼25 DNA strands. The covalent attachment of a shell of oligonucleotides to the surface of β-galactosidase enhances its cellular uptake of by up to ∼280-fold and allows for the use of working concentrations as low as 100 pM enzyme. DNA-functionalized β-galactosidase retains its ability to catalyze the hydrolysis of β-glycosidic linkages once endocytosed, whereas equal concentrations of protein show little to no intracellular catalytic activity.
authors.affiliation: International Institute of Nanotechnology, ‡Department of Chemistry, and §Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Brodin
authors.affiliation: International Institute of Nanotechnology, ‡Department of Chemistry, and §Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Sprangers
authors.affiliation: International Institute of Nanotechnology, ‡Department of Chemistry, and §Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: McMillan
authors.affiliation: International Institute of Nanotechnology, ‡Department of Chemistry, and §Department of Biomedical Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
mesh_terms: D002384:Catalysis; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D006801:Humans; D013056:Spectrophotometry, Ultraviolet; D001616:beta-Galactosidase / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004247:DNA; D001616:beta-Galactosidase