Abstract：
The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 hin vivoeven at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.
摘要：
基因治疗的兴起，解决了许多常规方法无法有效治疗的疾病。基因载体对于保护治疗基因并将其递送到靶位点非常重要。甘露醇修饰的聚乙烯亚胺（PEI）可以提高我们小组先前报道的基因转染效率。为了进一步控制和提高有效基因释放到作用位点,将二硫键引入甘露醇修饰的PEI中以构建新的非病毒基因载体PeiSM。筛选甘露醇与二硫键连接的程度。其中,中度甘露醇修饰的具有二硫键的聚乙烯亚胺（M-PeiSM）显示出最佳的转染效率，和显着增强长期系统性转基因表达72小时在体内即使在单剂量给药，并且可以通过上调caveolin-1的磷酸化来促进caveole介导的摄取，并增加高GSH细胞内环境中纳米复合物的负载基因释放。这种功能化的基因递送系统可以用作进一步基因治疗的潜在和安全的非病毒纳米载体。
