Controlled Release of DNA from Surfaces

DNA 从表面的受控释放

• 批准号: 6734787
• 负责人: DAVID M LYNN
• 金额: $ 23.82万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6734787
• 关键词: DNA; bioengineering /biomedical engineering; biomaterial development /preparation; biotechnology; gene delivery system; gene therapy; molecular film; nanotechnology; plasmids; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): The broad goal of our research is the design of materials that control the distribution and release of DNA from the surfaces of biomedical materials and devices. The safe, efficient, and controlled delivery of DNA to cells presents a formidable challenge and an obstacle to the clinical success of gene therapy. Conventional materials do not meet the technical or clinical demands of this rapidly growing field, particularly for applications that require release from surfaces or the predictable administration of multiple gene sequences. Degradable polymer matrices can be engineered to sustain the release of plasmid DNA using strategies similar to those previously developed for the delivery of proteins. However, these bulk materials lack the sophistication required to control the distribution of plasmid (or multiple plasmids) near the surface of the material. We have developed degradable multilayered materials that provide nanometer-scale control over the incorporation and subsequent release of polyanions, including DNA. This proposal is based on the hypothesis that multilayered polymer assemblies incorporating plasmid DNA can be used to direct the release of DNA to cells growing on the surfaces of these materials. The following Specific Aims are designed to exhaustively evaluate this hypothesis. They are: 1) To incorporate plasmid DNA into hydrolytically degradable polyelectrolyte films using a layer-by-layer approach, 2) To characterize the physical and chemical erosion profiles of plasmid-containing films and establish the structural integrity of released DNA, and 3) To evaluate functional DNA-containing films as substrates for cell attachment and as platforms to direct the transfection of adherent cells. Sophisticated new materials that control the distribution and release of plasmid DNA from the surfaces of biomedical materials will have a profound impact on the development of localized gene therapies and the continued advance of gene therapy into the clinic.

描述（由申请人提供）：我们研究的广泛目标是设计材料，这些材料控制了从生物医学材料和设备表面的DNA分布和释放的材料。 DNA向细胞的安全，高效和受控的传递带来了巨大的挑战和基因治疗临床成功的障碍。 常规材料不满足这个快速增长的领域的技术或临床需求，特别是对于需要从表面释放或可预测的多个基因序列施用的应用。 可以使用类似于先前用于蛋白质递送的策略来设计可降解的聚合物矩阵，以维持质粒DNA的释放。 但是，这些大量材料缺乏控制材料表面附近质粒（或多种质粒）分布所需的复杂性。 我们已经开发了可降解的多层材料，可对纳米尺度进行对掺入和随后释放的多个材料（包括DNA）的控制。 该建议基于以下假设：包含质粒DNA的多层聚合物组件可用于将DNA释放到生长在这些材料表面上的细胞。 以下特定目标旨在详尽评估这一假设。 它们是：1）使用逐层方法将质粒DNA纳入可降解的聚电解质膜中，2）表征含质粒膜的物理和化学侵蚀曲线，并建立释放的DNA的结构完整性，并建立供应型单元格的型单元格的型单元格，并建立3），以评估供应型单元格的型单元格，并将其用于供应。 控制质粒DNA从生物医学材料表面的分布和释放的复杂新材料将对局部基因疗法的发展产生深远的影响，并持续发展基因疗法进入诊所。