利用RGD和HIV Tat肽功能化的聚合物纳米颗粒将基因传递至分化的神经典型细胞。
Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles.
作者信息
Suk Jung Soo, Suh Junghae, Choy Kokleong, Lai Samuel K, Fu Jie, Hanes Justin
机构信息
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
出版信息
Biomaterials. 2006 Oct;27(29):5143-50. doi: 10.1016/j.biomaterials.2006.05.013.
Abstract
A number of neurodegenerative disorders may potentially be treated by the delivery of therapeutic genes to neurons. Nonviral gene delivery systems, however, typically provide low transfection efficiency in post-mitotic differentiated neurons. To uncover mechanistic reasons for this observation, we compared gene transfer to undifferentiated and differentiated SH-SY5Y cells using polyethylenimine (PEI)/DNA nanocomplexes. Differentiated cells exhibited substantially lower uptake of gene vectors. To overcome this bottleneck, RGD or HIV-1 Tat peptides were attached to PEI/DNA nanocomplexes via poly(ethylene glycol) (PEG) spacer molecules. Both RGD and Tat improved the cellular uptake of gene vectors and enhanced gene transfection efficiency of primary neurons up to 14-fold. RGD functionalization resulted in a statistically significant increase in vector escape from endosomes, suggesting it may improve gene delivery by more than one mechanism.
摘要
多种神经退行性疾病可能通过向神经元递送治疗性基因来进行治疗。然而，非病毒基因递送系统通常在有丝分裂后分化的神经元中提供较低的转染效率。为了揭示这一现象背后的机制，我们使用聚乙烯亚胺（PEI）/DNA纳米复合物，比较了未分化和分化的SH-SY5Y细胞的基因转移情况。分化细胞对基因载体的摄取显著降低。为了克服这一瓶颈，将RGD或HIV-1 Tat肽通过聚乙二醇（PEG）间隔分子连接到PEI/DNA纳米复合物上。RGD和Tat都提高了基因载体的细胞摄取，并将原代神经元的基因转染效率提高了14倍。RGD功能化导致载体从内体逃逸的统计学显著增加，表明它可能通过多种机制改善基因递送。
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