Multilayer Nanocomplexes of Polymer and DNA Exhibit Enhanced Gene Delivery


  • J.M.S. and C.-H.K.W. contributed equally to this work. This work was supported by the National Hemophilia Foundation and the Alliance for Cancer Gene Therapy. Confocal microscopy images were acquired at the University of Washington's Nanotech User Facility, which is supported by the National Science Foundation and the Center for Nanotechnology at the University of Washington. TEM images were acquired at the University of Washington's Pathology Electron Microscopy Center. Flow cytometry was performed in the Department of Immunology at the University of Washington, School of Medicine. We are grateful to William Bernt (Brookhaven Instruments) for his assistance in the analysis of light scattering data, and to manuscript reviewers for helpful suggestions. Supporting Information is available online from Wiley InterScience or from the authors.


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Polymeric-DNA complexes (polyplexes) are constructed with multiple layers of counter-polyions as DNA/polyethylenimine/poly(acrylic acid)/polyethylenimine. The increased association of polyethylenimine achieved by the multilayer approach leads to substantial increases in expression of transgene for reporter plasmids without the need for excess free polymer typically required for non-viral gene delivery. This method of polyplex preparation provides the opportunity to improve transgene expression for gene therapy approaches to disease treatment.