Luo Dan, Han Ernest, Belcheva Nadya, Saltzman W Mark
School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
J Control Release. 2004 Mar 5;95(2):333-41. doi: 10.1016/j.jconrel.2003.11.019.
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.
由于对病毒DNA递送系统的毒性和免疫原性的担忧日益增加，通过非病毒途径进行DNA递送变得更具吸引力和优势。理想的非病毒DNA递送系统应该是一种模拟病毒载体的合成系统。它还应该具有生物相容性、高效性和模块化，以便能够针对研究和临床环境中的各种应用进行调整。朝着这种模块化合成DNA递送系统迈出的第一个成功步骤得到了证明：一种由二氧化硅纳米颗粒介导的三组分转染系统。致密的二氧化硅纳米颗粒通过在细胞表面物理聚集作为摄取增强组分；几乎用每种测试的转染试剂都能观察到由于颗粒导致的转染增强，且毒性很小。此外，已经建立了一个数学模型，该模型成功预测了转染增强的几个重要参数。这种三组分转染系统为未来可能用于非病毒基因治疗和DNA疫苗接种的多组分模块化合成DNA递送系统奠定了基础。
