Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
Mol Pharm. 2012 Nov 5;9(11):3099-106. doi: 10.1021/mp300231d. Epub 2012 Oct 11.
Gene therapy is a field that offers hope and promise for the treatment of diseases and traumas of a genetic nature and otherwise. However, progress toward the clinic has been delayed because of concerns over the safety of viral vectors and the efficacy of safer nonviral systems, which have low transfection efficacy and short transgene expression. This study describes the fabrication and characterization of a safe gene delivery reservoir system that has the potential to overcome issues associated with nonviral systems. Harnessing the electrostatic charges of collagen and polystyrene, microspheres were fabricated using a template-based method and characterized by microscopy techniques such as scanning electron microscopy, transmission electron microscopy, and atomic force microscopy, with the removal of the polystyrene template confirmed by Fourier transform infrared spectroscopy analysis. Loading and release of polyplexes confirmed the ability of the system to prolong polyplex delivery, with minimal cytotoxicity observed from viability studies on 3T3 fibroblasts. Finally, biological activity of released polyplexes was confirmed by reporter gene expression. Taken together, these properties indicate the potential of this system as a reservoir for gene delivery.
基因治疗为治疗遗传和非遗传性质的疾病和创伤提供了希望和承诺。然而，由于对病毒载体的安全性和更安全的非病毒系统的功效的担忧，向临床的进展已经被延迟，因为非病毒系统的转染效率低和转基因表达时间短。本研究描述了一种安全的基因传递储库系统的制造和特性，该系统有可能克服与非病毒系统相关的问题。利用胶原蛋白和聚苯乙烯的静电电荷，使用基于模板的方法制造微球，并通过显微镜技术（如扫描电子显微镜、透射电子显微镜和原子力显微镜）进行表征，通过傅里叶变换红外光谱分析证实了聚苯乙烯模板的去除。多聚物的负载和释放证实了该系统能够延长多聚物的传递，在对 3T3 成纤维细胞进行的生存力研究中观察到最小的细胞毒性。最后，通过报告基因表达证实了释放的多聚物的生物学活性。综上所述，这些特性表明该系统作为基因传递储库的潜力。
