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）：我们研究的主要目标是设计控制 DNA 从生物医学材料和设备表面分布和释放的材料。 安全、高效、可控地将 DNA 递送至细胞是基因治疗临床成功的巨大挑战和障碍。 传统材料无法满足这个快速发展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地施用多个基因序列的应用。 可降解聚合物基质可采用与之前开发的蛋白质递送类似的策略来设计以维持质粒 DNA 的释放。 然而，这些散装材料缺乏控制材料表面附近的质粒（或多个质粒）分布所需的复杂性。 我们开发了可降解的多层材料，可以对聚阴离子（包括 DNA）的掺入和随后的释放进行纳米级控制。 该提议基于这样的假设：掺入质粒 DNA 的多层聚合物组件可用于引导 DNA 释放到在这些材料表面生长的细胞中。 以下具体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 掺入可水解降解的聚电解质膜中，2) 表征含质粒膜的物理和化学侵蚀特征并建立释放 DNA 的结构完整性，以及 3)评估功能性含 DNA 薄膜作为细胞附着基质和指导贴壁细胞转染的平台。 控制质粒DNA从生物医学材料表面分布和释放的复杂新材料将对局部基因疗法的发展以及基因疗法进入临床的持续推进产生深远的影响。