A Degradable Polyethylenimine Derivative with Low Toxicity for Highly Efficient Gene Delivery

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• 作者：M. Laird Forrest ; James T. Koerber ; and Daniel W. Pack
• 刊名：Bioconjugate Chemistry
• 出版年：2003
• 出版时间：September 2003
• 年：2003
• 卷：14
• 期：5
• 页码：934 - 940
• 全文大小：124K
• 年卷期：v.14,no.5(September 2003)
• ISSN：1520-4812

文摘

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 providingtargeting, low immunogenicity, nontoxicity, and robustness, but lack sufficient gene delivery efficiency.We have synthesized a versatile group of degradable polycations, through addition of 800-Dapolyethylenimine (PEI) to small diacrylate cross-linkers. The degradable polymers reported here aresimilar 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 dateand provide a versatile platform for investigation of the effects of polymer structure and degradationrate on gene delivery efficiency.