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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 ?-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 ?-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 ?-galactosidase retains its ability to catalyze the hydrolysis of ?-glycosidic linkages once endocytosed, whereas equal concentrations of protein show little to no intracellular catalytic activity.

SUBMITTER: Brodin JD

PROVIDER: S-EPMC5831182 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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DNA-Mediated Cellular Delivery of Functional Enzymes.

Brodin Jeffrey D JD Sprangers Anthony J AJ McMillan Janet R JR Mirkin Chad A CA

Journal of the American Chemical Society 20151120 47

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 up ...[more]

PMID: 26587747

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