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Use of Primary and Secondary Polyvinylamines for Efficient Gene Transfection

机译:使用初级和二级聚乙烯胺进行高效基因转染

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摘要

Gene transfection with polymeric carrier remains a challenge; particularly, high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected family of cationic polymers. They can be readily obtained by controlled hydrolysis of polyvinylamides prepared through (controlled) radical polymerization. A series of tailor-made and well-defined polyvinylamines bearing primary amino groups, and poly(N-methylvinylamine) bearing secondary amines, were evaluated for the transfection of cells with pDNA as a function of their molar mass, molar mass distribution, and degree of deacetylation. Unexpected high transfection levels, in combination with low cytotoxicity were recorded for both series. Surprisingly, a great impact of the molar mass was observed for the primary amine polyvinylamine series, whereas the results were mostly independent of molar mass or dispersity for the polymer bearing secondary amine. It was further established that a certain percentage of acetamide groups increased the transfection level, while maintaining low cytotoxicity. These results highlight for the first time the real potential of polyvinylamines as gene carriers, and make these polymers very attractive for further development in gene therapy.
机译:与聚合物载体的基因转染仍然是一个挑战;特别是,难以实现高毒性的高转染水平。我们在此recisit polyvinylamines,旧的和被忽略的阳离子聚合物家族。可以通过通过(控制)自由基聚合制备的聚乙烯酰胺的受控水解可以容易地获得。评估亚氨基和聚(N-甲基丙胺)和聚(N-甲基丙胺)的一系列定义和明确定义的聚乙烯醇含有仲胺,以与其摩尔质量,摩尔质量分布和程度的函数转染细胞脱乙酰化。两种系列记录出意外的高转染水平,与低细胞毒性结合。令人惊讶的是,对伯胺聚乙烯胺系列观察到摩尔物质的巨大影响,而结果主要与含有仲胺的聚合物的摩尔质量或分散性无关。进一步确定,一定百分比的乙酰胺基团增加了转染水平,同时保持低细胞毒性。这些结果首次突出了聚乙烯胺作为基因载体的真正潜力,并使这些聚合物非常吸引于基因治疗中的进一步发展。

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  • 来源
    《Biomacromolecules》 |2017年第2期|共12页
  • 作者单位

    UPMC Univ Paris 06 Sorbonne Univ CNRS Inst Parisien Chim Mol Equipe Chim Polymeres 4 Pl Jussieu F-75005 Paris France;

    Univ Liege ULg Dept Chem CERM Allee Chim 3 B-4000 Liege Belgium;

    CNRS Ctr Biophys Mol UPR4301 Rue Charles Sadron F-45071 Orleans 2 France;

    Univ Liege ULg Dept Chem CERM Allee Chim 3 B-4000 Liege Belgium;

    CNRS Ctr Biophys Mol UPR4301 Rue Charles Sadron F-45071 Orleans 2 France;

    UPMC Univ Paris 06 Sorbonne Univ CNRS Inst Parisien Chim Mol Equipe Chim Polymeres 4 Pl Jussieu F-75005 Paris France;

    UPMC Univ Paris 06 Sorbonne Univ CNRS Inst Parisien Chim Mol Equipe Chim Polymeres 4 Pl Jussieu F-75005 Paris France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

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