Controlled Release of DNA from Surfaces
DNA 从表面的受控释放
基本信息
- 批准号:6798605
- 负责人:
- 金额:$ 22.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-09-05 至 2006-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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控制生物医学材料和器械表面DNA分布和释放的材料。 安全、有效和受控地将DNA递送到细胞是基因治疗临床成功的一个巨大挑战和障碍。 传统材料不能满足这一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。 可降解的聚合物基质可以被工程化以使用类似于先前开发的用于递送蛋白质的策略来维持质粒DNA的释放。 然而,这些散装材料缺乏控制材料表面附近质粒(或多个质粒)分布所需的复杂性。 我们已经开发出可降解的多层材料,提供纳米级的控制聚阴离子,包括DNA的掺入和随后的释放。 该提议基于这样的假设:掺入质粒DNA的多层聚合物组装体可用于引导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掺入到水解可降解的生物膜中,2)表征含质粒膜的物理和化学侵蚀概况并建立释放的DNA的结构完整性,和3)评估功能性含DNA膜作为细胞附着的基底和作为指导粘附细胞转染的平台。 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治疗的发展和基因治疗进入临床的持续发展产生深远影响。
项目成果
期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Apparent dewetting of ultrathin multilayered polyelectrolyte films incubated in aqueous environments.
- DOI:10.1021/la701720k
- 发表时间:2007-10
- 期刊:
- 影响因子:0
- 作者:Jingtao Zhang;N. Fredin;D. M. Lynn
- 通讯作者:Jingtao Zhang;N. Fredin;D. M. Lynn
Surface-Mediated Delivery of DNA: Cationic Polymers Take Charge.
- DOI:10.1016/j.cocis.2008.03.005
- 发表时间:2008-12
- 期刊:
- 影响因子:8.9
- 作者:Jewell CM;Lynn DM
- 通讯作者:Lynn DM
Multilayered Films Fabricated from Combinations of Degradable Polyamines: Tunable Erosion and Release of Anionic Polyelectrolytes.
由可降解聚胺组合制成的多层薄膜:可调阴离子聚电解质的侵蚀和释放。
- DOI:10.1021/ma061815g
- 发表时间:2006
- 期刊:
- 影响因子:5.5
- 作者:Zhang,Jingtao;Lynn,DavidM
- 通讯作者:Lynn,DavidM
Assembly of erodible, DNA-containing thin films on the surfaces of polymer microparticles: toward a layer-by-layer approach to the delivery of DNA to antigen-presenting cells.
- DOI:10.1016/j.actbio.2008.08.022
- 发表时间:2009-03
- 期刊:
- 影响因子:9.7
- 作者:Saurer, Eric M.;Jewell, Christopher M.;Kuchenreuther, Jon M.;Lynn, David M.
- 通讯作者:Lynn, David M.
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DAVID M LYNN其他文献
DAVID M LYNN的其他文献
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{{ truncateString('DAVID M LYNN', 18)}}的其他基金
Slippery Nanoemulsion-Infused Polymer Coatings that Prevent Bacterial Fouling and Block Bacterial Virulence
光滑的纳米乳液注入聚合物涂层可防止细菌污染并阻止细菌毒力
- 批准号:
10667161 - 财政年份:2023
- 资助金额:
$ 22.67万 - 项目类别:
Spatial and Temporal Control of Transfection Using Ferrocene-Containing Lipids
使用含二茂铁的脂质进行转染的空间和时间控制
- 批准号:
7385610 - 财政年份:2007
- 资助金额:
$ 22.67万 - 项目类别:
Spatial and Temporal Control of Transfection Using Ferrocene-Containing Lipids
使用含二茂铁的脂质进行转染的空间和时间控制
- 批准号:
7491650 - 财政年份:2007
- 资助金额:
$ 22.67万 - 项目类别:
BIODEGRADABLE PROTON SPONGES FOR GENE THERAPY
用于基因治疗的可生物降解质子海绵
- 批准号:
6385104 - 财政年份:1999
- 资助金额:
$ 22.67万 - 项目类别:
BIODEGRADABLE PROTON SPONGES FOR GENE THERAPY
用于基因治疗的可生物降解质子海绵
- 批准号:
6014592 - 财政年份:1999
- 资助金额:
$ 22.67万 - 项目类别: