Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Int J Pharm. 2012 Oct 15;436(1-2):555-63. doi: 10.1016/j.ijpharm.2012.07.001. Epub 2012 Jul 13.
Viral vectors, except for their safety concern, have shown high efficiency in both delivery and expression of gene. Here, a series of new gene carriers, comprised of short peptide subunits with special functions to imitate viral vectors, were designed and three vectors, (C(18))(2)KH(4)R(8)GDS, AcKH(4)R(8)GDS and (C(18))(2)KH(4)R(8), designated as ARM1, ARM2, ARM3, respectively, were synthesized and evaluated. The transfection efficiency in vitro was studied in terms of 293T, HepG2 and HeLa cell lines. It was found that the transfection efficiency was enhanced significantly for the vectors (ARM1 and ARM3) with double hydrophobic aliphatic tails. Interestingly, the conjugation of RGDS sequence in vectors displayed no obvious difference in cell adhesion for all of the three cell lines. Moreover, confocal laser scanning microscope results indicated that the peptide/pDNA complexes can enter the cell and nuclei successfully. On the other hand, all the vectors displayed low cytotoxicity. The artificial recombinant multi-block oligopeptides (ARMs) demonstrated here might give a promising potential of the peptide-based vectors in gene therapy.
病毒载体除了存在安全性问题外,在基因的传递和表达方面显示出了很高的效率。在这里,设计了一系列由具有模仿病毒载体特殊功能的短肽亚基组成的新型基因载体,合成了三种载体,(C(18))(2)KH(4)R(8)GDS、AcKH(4)R(8)GDS 和(C(18))(2)KH(4)R(8),分别命名为 ARM1、ARM2 和 ARM3,并对其进行了评估。通过 293T、HepG2 和 HeLa 细胞系研究了体外转染效率。结果发现,具有双疏水性脂肪族尾巴的载体(ARM1 和 ARM3)的转染效率显著提高。有趣的是,载体中 RGDS 序列的缀合对所有三种细胞系的细胞黏附均无明显差异。此外,共聚焦激光扫描显微镜结果表明,肽/pDNA 复合物可以成功进入细胞和细胞核。另一方面,所有载体均显示出低细胞毒性。这里展示的人工重组多嵌段寡肽(ARMs)可能为基于肽的载体在基因治疗中提供了有前途的潜力。