DNA-Mediated Cellular Delivery of Functional Enzymes
- 20 November 2015
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 137 (47), 14838-14841
- https://doi.org/10.1021/jacs.5b09711
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.Funding Information
- NTU-Northwestern Institute for Nanomedicine
- U.S. Department of Defense (N00014-15-1-0043)
- National Cancer Institute (U54 CA151880)
- National Science Foundation
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