CATIONIC LIPID PHASE BEHAVIOR AND ITS IMPORTANCE TO TRANSFECTION

阳离子脂质相行为及其对转染的重要性

• 批准号: 7601748
• 负责人: RUMIANA D TENCHOV
• 金额: $ 1.18万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601748
• 关键词: Affect; Behavior; Biological; Cells; Charge; Chemical Structure; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; Evolution; Funding; Grant; Institution; Light; Lipids; Membrane Lipids; Phase; Process; Property; Research; Research Personnel; Resources; Source; Structure; Transfection; United States National Institutes of Health; Viral Genes; gene therapy; lipofection

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Positively charged lipids can be used to deliver DNA to cells, and are considered the most promising non-viral gene carriers. They form complexes (lipoplexes) with the polyanionic DNA. The mechanism of lipofection is still largely unknown and the long-term objective of the project is to shed light on the lipofection mechanisms so that lipoplexes can be formulated with optimum efficiency for gene therapy. Although lamellar phases are most familiar due to their relationship to biological membranes, lipids form variety of nonlamellar phases as well. Phase state affects virtually all properties of lipid dispersions, and has been found to influence lipofection efficiency. This project is focused on the relationship between lipid phase behavior and transfection, in particular on understanding how DNA is discharged from lipoplexes, and how that process relates to the phase behavior of carrier lipid/cellular lipid arrays. The project is predicated on the hypothesis that a key factor for DNA release in transfection is the structural evolution of the lipoplexes upon interaction with cellular lipids, and that the initial lipoplex structure is mainly important for the successful import of DNA to cells. Preliminary results revealed correlation between DNA release and phases formed in mixtures of cellular and cationic lipids. The specific aims include understanding the mechanism of DNA release from lipoplexes induced by cellular lipid mixtures, and looking for correlation of the cationic lipids chemical structure, their phase organization, and the efficiency of DNA release by cellular lipids, so that lipoplexes of predicted superior transfection efficacy can be formulated.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 带正电荷的脂质可用于将DNA递送至细胞，并被认为是最有前途的非病毒基因载体。它们与聚阴离子 DNA 形成复合物（脂质复合物）。脂转染的机制仍然很大程度上未知，该项目的长期目标是阐明脂转染机制，以便能够以最佳效率配制脂质复合物用于基因治疗。尽管层状相因其与生物膜的关系而最为人们所熟知，但脂质也形成各种非层状相。相态几乎影响脂质分散体的所有特性，并且已被发现影响脂转染效率。该项目的重点是脂质相行为与转染之间的关系，特别是了解 DNA 如何从脂质复合物中排出，以及该过程如何与载体脂质/细胞脂质阵列的相行为相关。该项目基于这样的假设：转染中 DNA 释放的关键因素是脂复合物在与细胞脂质相互作用时的结构进化，并且初始脂复合物结构对于 DNA 成功导入细胞至关重要。初步结果揭示了 DNA 释放与细胞和阳离子脂质混合物中形成的相之间的相关性。具体目标包括了解细胞脂质混合物诱导的脂质复合物释放DNA的机制，并寻找阳离子脂质化学结构、其相组织和细胞脂质释放DNA的效率之间的相关性，从而可以配制具有预测的优异转染功效的脂质复合物。