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合成聚-β-氨基乙与醇反应性侧链,用于DNA输送

Gregory T Zugates¹, Daniel G Anderson, Steven R Little

¹Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building E25-342, Cambridge, MA 02139, USA.

Journal of the American Chemical Society

|September 28, 2006

概括

新型生物降解聚合物为基因治疗中安全高效的DNA输送提供了有前途的解决方案. 这些多β-氨基对细胞内条件做出反应,有助于基因解包装和减少毒性.

科学领域:

生物材料科学生物材料科学
基因治疗基因治疗
聚合物化学聚合物化学

背景情况:

非病毒基因疗法在临床应用中安全高效的DNA输送方面面临重大挑战.
开发有效且无毒的输送工具对于推进基因疗法至关重要.
可生物降解的聚合物为治疗应用提供了先进材料的潜力.

研究的目的:

开发新的,可生物降解的聚合物,以改善基因传递.
创建具有移植修饰能力和对细胞内条件的反应能力的聚合物.
研究新聚合物衍生物的DNA结合,复合形成和转染效率.

主要方法:

使用2-pyridyldithio) -ethylamine (PDA) 单体合成多-β-氨基.
聚合物的修饰用醇连接物 (甲胺和RGDC).
通过电泳和染料排除试验评估DNA结合;聚合物-DNA复合物的表征;评估细胞毒性和转染效率.

主要成果:

合成的阴离子,可降解的聚合物,具有具有表现出与醇连接体具有特定反应性的pyridyldithio功能.
经过强烈的DNA结合和自我组装,形成与等离子体DNA的阴离子复合体 (低至100nm).
在对细胞内谷氨的反应中观察到DNA结合的减少,这表明细胞内解封的潜力.
在人类肝细胞癌细胞中实现了与PEI相当的转染效率,观察到的细胞毒性较低.

结论:

基于PDA的多β-氨基是一种多功能平台,用于聚合物介导的基因传递.
开发的聚合物显示出,由于其可降解性,响应性和有效的转染能力,可确保安全和高效的DNA传递.
这些发现支持这些新型可生物降解聚合物的基因治疗中的潜在临床应用.

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