A self-assembled, modular DNA delivery system mediated by silica nanoparticles.

Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via non-viral routes has become more desirable and advantageous. The ideal non-viral DNA delivery system should be a synthetic system that mimics viral vectors. It should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The first successful step towards this modular synthetic DNA delivery system is demonstrated: a three-component transfection system mediated by silica nanoparticles. Dense silica nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface; enhanced transfection due to the particles is seen with almost every transfection reagent tested with little toxicity. In addition, a mathematical model has been built that successfully predicts several important parameters of transfection enhancement. This three-component transfection system lays the groundwork for a future multi-component modular synthetic DNA delivery system that may be useful in non-viral gene therapy and DNA vaccination.