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A polyethylenimine-mimetic biodegradable polycation gene vector and the effect of amine composition in transfection efficiency

机译:聚乙烯亚胺模拟可生物降解的聚阳离子基因载体及胺组成对转染效率的影响

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摘要

The low toxicity and efficient gene delivery of polymeric vectors remain the major barrier to the clinical application of non-viral gene therapy. Here, we present a poly-d, l-succinimide (PSI)-based biodegradable cationic polymer which mimicked the golden standard, branched polyethylenimine (PEI, ~25 kDa). To investigate the influence of 1°, 2°, 3° amine group ratio in the polymer, a series of PSI-based vectors (PSI-NN'x-NNy) grafted with different amine side chains of N,N-dimethyldipropylenetriamine (NN') and bis(3-aminopropyl)amine (NN) were first characterized and contrasted by biophysical measurements. The in vitro and in vivo biological assay demonstrated that PSI-NN'0.85-NN1 exhibited better transfection ability and biocompatibility than PEI. The present results suggest that such PEI-mimic biodegradable PSI-NN'0.85-NN1 possesses a good potential application for clinical gene delivery.
机译:聚合载体的低毒性和有效的基因传递仍然是非病毒基因疗法临床应用的主要障碍。在这里,我们介绍了一种基于聚-d-琥珀酰亚胺(PSI)的可生物降解阳离子聚合物,它模仿了金标准支化聚乙烯亚胺(PEI,〜25 kDa)。为了研究1°,2°,3°胺基团比例对聚合物的影响,一系列接枝了N,N-二甲基二丙烯三胺(NN)不同胺侧链的基于PSI的载体(PSI-NN'x-NNy) )和双(3-氨基丙基)胺(NN)首先通过生物物理测量进行表征和对比。体外和体内生物学测定表明,PSI-NN'0.85-NN1比PEI表现出更好的转染能力和生物相容性。目前的结果表明,这种可模仿PEI的可生物降解的PSI-NN'0.85-NN1在临床基因递送方面具有良好的潜在应用。

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