Mannose polyethylenimine conjugates for targeted DNA delivery into dendritic cells

Cell surface-bound receptors represent suitable entry sites for gene delive ry into cells by receptor-mediated endocytosis. Here we have taken advantag e of the mannose receptor that is highly expressed on antigen-presenting de ndritic cells for targeted gene transfer by employing mannosylpolyethylenim ine (ManPEI) conjugates. Several ManPEI conjugates were synthesized and use d for formation of ManPEI/DNA transfection complexes. Conjugates differed i n the Linker between mannose and polyethylenimine (PEI) and in the size of the PEI moiety. We demonstrate that ManPEI transfection is effective in del ivering DNA into mannose receptor-expressing cells. Uptake of ManPEI/DNA co mplexes is receptor-specific, since DNA delivery can be competed with manno sylated albumin, Additionally, incorporation of adenovirus particles into t ransfection complexes effectively enhances transgene expression. This is pa rticularly important for primary immunocompetent dendritic cells. It is dem onstrated here that dendritic cells transfected with ManPEI/DNA complexes c ontaining adenovirus particles are effective in activating T cells of T cel l receptor transgenic mice in an antigen-specific fashion.