A degradable polyethylenimine derivative with low toxicity for highly efficient gene delivery
A degradable polyethylenimine derivative with low toxicity for highly efficient gene delivery
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DOI：
10.1021/bc034014g
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发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Pack, DW
中科院分区：
文献类型：
--
作者：
Forrest, ML;Koerber, JT;Pack, DW
人类基因治疗的常规临床实施需要安全有效的基因传递方法。由于多种化学物质的可用性，聚合载体具有潜在的靶向性、低免疫原性、无毒性和稳健性，但缺乏足够的基因传递效率，因此前景广阔。我们通过将800-Da聚乙烯亚胺（PEI）添加到小的二丙烯酸酯交联剂中，合成了一组多功能的可降解聚阳离子。本文报道的可降解聚合物在结构、大小（14-30 kDa）和dna结合特性上与市购的25 kDa PEI相似，但介导基因表达的效率提高了2 - 16倍，而且基本上无毒。这些容易合成的聚合物是迄今为止报道的最有效的聚合物载体，为研究聚合物结构和降解率对基因传递效率的影响提供了一个通用的平台。
Routine clinical implementation of human gene therapy awaits safe and efficient gene delivery methods. Polymeric vectors hold promise due to the availability of diverse chemistries, potentially providing targeting, low immunogenicity, nontoxicity, and robustness, but lack sufficient gene delivery efficiency. We have synthesized a versatile group of degradable polycations, through addition of 800-Da polyethylenimine (PEI) to small diacrylate cross-linkers. The degradable polymers reported here are similar in structure, size (14-30 kDa), and DNA-binding properties to commercially available 25-kDa PEI, but mediate gene expression two- to 16-fold more efficiently and are essentially nontoxic. These easily synthesized polymers are some of the most efficient polymeric vectors reported to date and provide a versatile platform for investigation of the effects of polymer structure and degradation rate on gene delivery efficiency.