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J Biol Chem, Vol. 274, Issue 27, 19087-19094, July 2, 1999

Mannose Polyethylenimine Conjugates for Targeted DNA Delivery into Dendritic Cells

Sandra S. Diebold, Margaretha Kursa^§, Ernst Wagner^§, Matt Cotten^¶, and Martin Zenke

From the  Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13092 Berlin, Germany, ^§ Boehringer Ingelheim Austria, Dr. Boehringer-Gasse 5-11, A-1121 Vienna, Austria, and the ^¶ Institute for Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria

Cell surface-bound receptors represent suitable entry sites for gene delivery into cells by receptor-mediated endocytosis. Here we have taken advantage of the mannose receptor that is highly expressed on antigen-presenting dendritic cells for targeted gene transfer by employing mannosylpolyethylenimine (ManPEI) conjugates. Several ManPEI conjugates were synthesized and used for formation of ManPEI/DNA transfection complexes. Conjugates differed in the linker between mannose and polyethylenimine (PEI) and in the size of the PEI moiety. We demonstrate that ManPEI transfection is effective in delivering DNA into mannose receptor-expressing cells. Uptake of ManPEI/DNA complexes is receptor-specific, since DNA delivery can be competed with mannosylated albumin. Additionally, incorporation of adenovirus particles into transfection complexes effectively enhances transgene expression. This is particularly important for primary immunocompetent dendritic cells. It is demonstrated here that dendritic cells transfected with ManPEI/DNA complexes containing adenovirus particles are effective in activating T cells of T cell receptor transgenic mice in an antigen-specific fashion.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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