Department of Pathology, The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Gene Ther. 2011 Mar;18(3):220-4. doi: 10.1038/gt.2010.123. Epub 2010 Oct 21.
This work illustrates the utility of Minivector DNA, a non-viral, supercoiled gene therapy vector incorporating short hairpin RNA from an H1 promoter. Minivector DNA is superior to both plasmid DNA and small interfering RNA (siRNA) in that it has improved biostability while maintaining high cell transfection efficiency and gene silencing capacity. Minivector DNAs were stable for over 48 h in human serum, as compared with only 0.5 and 2 h for siRNA and plasmid, respectively. Although all three nucleic acids exhibited similar transfection efficiencies in easily transfected adhesion fibroblasts cells, only Minivector DNAs and siRNA were capable of transfecting difficult-to-transfect suspension lymphoma cells. Minivector DNA and siRNA were capable of silencing the gene encoding anaplastic lymphoma kinase, a key pathogenic factor of human anaplastic large cell lymphoma, and this silencing caused inhibition of the lymphoma cells. Based on these results, Minivector DNAs are a promising new gene therapy tool.
这项工作说明了 Minivector DNA 的实用性，它是一种非病毒、超螺旋的基因治疗载体，包含来自 H1 启动子的短发夹 RNA。与质粒 DNA 和小干扰 RNA (siRNA) 相比，Minivector DNA 具有更好的生物稳定性，同时保持了高细胞转染效率和基因沉默能力。与 siRNA 和质粒分别在人血清中仅稳定 0.5 和 2 小时相比，Minivector DNA 稳定超过 48 小时。尽管所有三种核酸在易于转染的贴壁成纤维细胞中都表现出相似的转染效率，但只有 Minivector DNA 和 siRNA 能够转染难以转染的悬浮淋巴瘤细胞。Minivector DNA 和 siRNA 能够沉默编码间变性淋巴瘤激酶的基因，间变性淋巴瘤激酶是人类间变性大细胞淋巴瘤的关键致病因素，这种沉默导致淋巴瘤细胞的抑制。基于这些结果，Minivector DNA 是一种很有前途的新型基因治疗工具。
