Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles
Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles
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DOI：
10.1016/j.biomaterials.2006.05.013
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发表时间：
2006-10-01
期刊：
影响因子：
14
通讯作者：
Hanes, Justin
中科院分区：
文献类型：
--
作者：
Suk, Jung Soo;Suh, Junghae;Hanes, Justin
许多神经退行性疾病可能通过向神经元输送治疗性基因来治疗。然而，非病毒基因传递系统在有丝分裂后分化的神经元中的转染率通常很低。为了揭示这一观察的机制原因，我们使用聚乙烯亚胺(PEI)/DNA纳米复合体比较了未分化和已分化的SH-SY5Y细胞的基因转移。分化后的细胞对基因载体的摄取显著降低。为了克服这一瓶颈，RGD或HIV-1Tat多肽通过聚乙二醇间隔物分子连接到PEI/DNA纳米复合体上。RGD和TAT都提高了细胞对基因载体的摄取，并将原代神经元的基因转染率提高了14倍。RGD功能化在统计上显著增加了载体逃避内小体的情况，这表明它可能通过多种机制改善基因传递。(C)2006爱思唯尔有限公司。保留所有权利。
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. (c) 2006 Elsevier Ltd. All rights reserved.