Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery.

Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Research Abstract Details 

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Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Abstract Text:

Gregory T Zugates,Daniel G Anderson,Steven R Little,Ingrid E B Lawhorn,Robert Langer,

The safe and efficient delivery of DNA remains the major barrier to the clinical application of non-viral gene therapy. Here, we present novel, biodegradable polymers for gene delivery that are capable of simple graft modification and demonstrate the ability to respond to intracellular conditions. We synthesized poly(beta-amino ester)s using a new amine monomer, 2-(pyridyldithio)-ethylamine (PDA). These cationic, degradable polymers contain pyridyldithio functionalities in the side chains that react with high specificity toward thiol ligands. This reactivity is demonstrated using both mercaptoethylamine (MEA) and the thiol peptide RGDC, a ligand that binds with high affinity to certain integrin receptors. These two polymer derivatives displayed strong DNA binding as determined using electrophoresis and dye exclusion assays. In addition, the MEA-based polymer and plasmid DNA were shown to self-assemble into cationic complexes with effective diameters as low as 100 nm. Furthermore, this DNA binding ability was substantially reduced in response to intracellular glutathione concentrations, which may aid in DNA unpackaging inside the cell. These complexes also displayed low cellular toxicity and were able to mediate transfection at levels comparable to PEI in human hepatocellular carcinoma cells. These results suggest that PDA-based poly(beta-amino ester)s may serve as a modular platform for polymer-mediated gene delivery.

Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Publishing Authors By Initials

GT Zugates,DG Anderson,SR Little,IE Lawhorn,R Langer,

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Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 128

Page Numbers: 12726-34

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ISSN: 0002-7863

DAY: 4

MONTH: Oct

YEAR: 2006

Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

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Grant and Affiliation Information for Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery.

AFFILIATION: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building E25-342, Cambridge, MA 02139, USA.

Country: United States

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MEDLINETA: J Am Chem Soc

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