Astrocytes, the “star-shaped” glial cells, are appealing gene-delivery targets to treat neurological diseases due to their diverse roles in brain homeostasis and disease. Cationic polymers have successfully delivered genes to mammalian cells and hence present a viable, non-immunogenic alternative to widely used viral vectors. In this study, we investigated the gene delivery potential of a series of arginine- and polyethylene glycol-modified, siloxane-based polyethylenimine analogs in primary cultured human neural cells (neurons and astrocytes) and in mice. Plasmid DNAs encoding luciferase reporter were used to measure gene expression. We hypothesized that polyplexes with arginine would help in cellular transport of the DNA, including across the blood-brain barrier; polyethylene glycol will stabilize polyethylenimine and reduce its toxicity while maintaining its DNA-condensing ability. Polyplexes were non-toxic to human neural cells and red blood cells. Cellular uptake of polyplexes and sustained gene expression were seen in human astrocytes as well as in mouse brains post-intravenous-injections. The polyplexes also delivered and expressed genes driven by astrocyte-restricted glial fibrillary acidic protein promoters, which are weaker than viral promoters. To our knowledge, the presented work validates a biocompatible and effective polymer-facilitated gene-delivery system for both human brain cells and mice for the first time.

星形胶质细胞，即“星形”神经胶质细胞，由于其在大脑稳态和疾病中的不同作用，成为治疗神经系统疾病的有吸引力的基因传递靶点。阳离子聚合物已成功地将基因传递至哺乳动物细胞，因此为广泛使用的病毒载体提供了一种可行的、非免疫原性的替代品。在这项研究中，我们研究了一系列精氨酸和聚乙二醇修饰的硅氧烷基聚乙烯亚胺类似物在原代培养的人类神经细胞（神经元和星形胶质细胞）和小鼠中的基因传递潜力。编码荧光素酶报告基因的质粒 DNA 用于测量基因表达。我们假设含有精氨酸的复合物将有助于 DNA 的细胞运输，包括穿过血脑屏障；聚乙二醇可以稳定聚乙烯亚胺并降低其毒性，同时保持其 DNA 浓缩能力。复合物对人类神经细胞和红细胞无毒。在人类星形胶质细胞以及静脉注射后的小鼠大脑中观察到了多聚复合物的细胞摄取和持续的基因表达。这些复合物还递送和表达由星形胶质细胞限制性神经胶质原纤维酸性蛋白启动子驱动的基因，该启动子比病毒启动子弱。据我们所知，所提出的工作首次验证了人类脑细胞和小鼠的生物相容性和有效的聚合物促进的基因传递系统。