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Issue 4, 2009
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Synergistic effects on gene delivery – co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000™

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Abstract

This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000™, a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000™ arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.

Graphical abstract: Synergistic effects on gene delivery – co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000™

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Publication details

The article was received on 20 Oct 2008, accepted on 01 Dec 2008 and first published on 12 Jan 2009


Article type: Paper
DOI: 10.1039/B818469K
Citation: Org. Biomol. Chem., 2009,7, 789-793
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    Synergistic effects on gene delivery – co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000™

    J. G. Hardy, C. S. Love, N. P. Gabrielson, D. W. Pack and D. K. Smith, Org. Biomol. Chem., 2009, 7, 789
    DOI: 10.1039/B818469K

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