Gemini surfactants: behaviour at interfaces and interaction with synthetic and biological macromolecules

Gemini 表面活性剂：界面行为以及与合成和生物大分子的相互作用

• 批准号: 5528-2007
• 负责人: Verrall, Ronald
• 金额: $ 2.55万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=389157
• 关键词: Gemini; surfactants; behaviour; interfaces; interaction

The Human Genome Mapping Project has allowed the identification of genes and gene defects implicated in a number of inherited diseases. Gene therapy represents the repair of defective protein expression in these diseases where there are no adequate therapies available. The basic idea is to replace the "sick" gene with a "healthy" one or to add a new gene to promote the synthesis of a therapeutic protein. The transfer of the gene (plasmid DNA) across the cell membrane to the target, transfection, has been mainly pursued using viral vectors with native DNA having been replaced by the required DNA. The procedures using such vectors are complex, hazardous, and expensive. Recently, nonviral vectors have been studied as alternate agents. We have found that surface active agents (soap-like) consisting of two positively charged head groups and two alkyl tails, connected by a hydrocarbon spacer group, can act as effective nonviral vectors. The complexes they form with DNA, in the presence of a "helper-lipid," have been shown by us to be able to express a therapeutic protein within certain cell lines. The objective of the next stage of research is to improve the transfection efficiency of these nonviral vectors; (i) by modifying the chemical structure of the surfactant so that the morphology of the resulting complex with DNA is better adapted to transfer through the cell membrane and (ii) to improve our insight of the mechanism of release of the DNA from the endosome once it is within the cell. The development of topical delivery systems for therapeutic agents is a priority area, worldwide, for public and animal health agencies. However, at this time there appears to be little Canadian-based research focusing on this activity. The project described here will be an important step in keeping Canada at the forefront of this research area.

人类基因组映射项目允许鉴定基因和基因缺陷，涉及许多遗传疾病。基因疗法代表了没有适当疗法的这些疾病中蛋白质表达有缺陷的修复。基本思想是用“健康”的基因代替“健康”基因，或添加新基因以促进治疗蛋白的合成。 基因（质粒DNA）跨细胞膜转移到靶标的转染，主要是使用本天然DNA的病毒载体被所需的DNA取代的病毒载体。使用此类矢量的程序是复杂，危险且昂贵的。最近，已经研究了非病毒载体作为备用药物。我们发现，由两个带正电荷的头部组和两个由碳氢化合物间隔组连接的烷基的头部组组成的表面活性剂（类似肥皂样）可以充当有效的非病毒载体。在存在“辅助脂质”的情况下，它们与DNA形成的复合物已证明我们能够在某些细胞系中表达治疗蛋白。下一阶段研究的目的是提高这些非病毒载体的转染效率。 （i）通过修饰表面活性剂的化学结构，以便将与DNA产生的复合物的形态更好地适应通过细胞膜转移，（ii）一旦细胞内的内体释放DNA的机理，可以提高我们对DNA释放机制的见解。用于治疗剂的局部交付系统的开发是全球公共和动物健康机构的优先领域。但是，目前似乎很少有基于加拿大的研究专注于这项活动。这里描述的项目将是将加拿大置于该研究领域的最前沿的重要一步。