Nanoscale Functional Dendrimer-DNA Assemblies

纳米级功能性树枝状聚合物-DNA 组装体

• 批准号: 7541466
• 负责人: MARK W. GRINSTAFF
• 金额: $ 16.25万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-04 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7541466
• 关键词: Address; Affect; Architecture; Basic Science; Benchmarking; Binding; Biological; Biological Assay; Biology; Biomimetics; Cancer Patient; Cells; Characteristics; Charge; Chromosomes; Classification; Cleaved cell; Colon Carcinoma; DNA; DNA Binding; DNA Packaging; Dendrimers; Development; Differential Scanning Calorimetry; Disease; Electrostatics; Endocytosis; Esters; Evaluation; Fluorescence Resonance Energy Transfer; Formazans; Future; Galactosidase; Gene Delivery; Gene Proteins; Generations; Genes; Genetic Transcription; Goals; Histones; Hydrogen Bonding; Hydrophobic Interactions; In Vitro; Investigation; Lead; Lipids; Medicine; Methods; Methylation; Microscopic; Molecular; NIH Program Announcements; Nanostructures; Nanotechnology; Non-Viral Vector; Nuclear; Pathway interactions; Patient Care; Phosphorylation; Play; Polymers; Preparation; Property; Proteins; Public Health; Reaction; Reporter Genes; Research; Research Personnel; Role; Safety; Shapes; Structure; System; TP53 gene; Techniques; Transfection; Transmission Electron Microscopy; Treatment Protocols; Tumor Suppressor Genes; Tumor Suppressor Proteins; Vaccines; Viral Vector; base; cancer cell; cancer therapy; colon cancer cell line; controlled release; cytotoxicity; database structure; design; esterase; gene therapy; histone modification; improved; innovation; insight; interest; macromolecule; nanoscale; nanoscience; novel; novel strategies; process optimization; programs; research clinical testing; response; synthetic construct; therapeutic gene; vector

This proposal describes the preparation and evaluation of new gene delivery vehicles composed of dendritic amphiphiles and DMA. These new functional dendritic amphiphiles undergo an electrostatic transition from cationic to anionic via an esterase-catalyzed reaction intracellularly to release DMA from the nanoscale assembly. We hypothesize that this change in electrostatic interactions with DNA will lead to increased gene transfection levels. A detailed, systematic investigation is proposed that entails the following three specific aims for this three-year R21 proposal: Aim 1. Determine the key molecular characteristics of the dendritic amphiphile required for binding and release of DNA. Aim 2. Characterize the nanoscale assemblies formed with the dendritic amphiphiles, and dendritic amphiphiles and DNA. Aim 3. Evaluate functional interactions of dendritic amphiphile/DNA assemblies with cells in vitro and deliver the p53 gene to colon cancer cells. The results of successful completion of this study will be: 1) one or more functional dendritic amphiphiles for delivery of the p53 gene to colon cancer cells; 2) a database of structure-property relationships; and 3) insight into the design of optimized dendritic vectors. These studies will also provide detailed physicochemical and biological information on this new class of dendritic amphiphiles and their corresponding assemblies, which is key for the future development of functional dendrimer/DNA assemblies for gene delivery. Relevance to Public Health: Innovative strategies to treat or cure colon cancer are still needed. Today, the current treatment protocols have resulted in improved patient care but the response rate remains only about 35% for metastatic colon cancer patients. In this proposal new well-defined polymers are described for the delivery of a tumor suppressor gene for the treatment of colon cancer.

该建议描述了由树突状组成的新基因输送车的准备和评估 两亲和DMA。这些新的功能性树枝状两亲物经历了从 通过酯酶催化的反应细胞内通过酯化反应从纳米级释放DMA 集会。我们假设与DNA静电相互作用的这种变化将导致基因增加 转染水平。提出了一项详细的系统调查，需要以下三个特定 为期三年的R21提案的目的： 目标1。确定结合和 DNA的释放。 AIM 2。特征是由树突两生和树突形成的纳米级组件 两亲和DNA。 AIM 3。评估树突两生/DNA组件与细胞体外的功能相互作用并提供 p53基因与结肠癌细胞。 这项研究成功完成的结果将是：1）一个或多个功能性树枝状两亲物。 将p53基因递送至结肠癌细胞； 2）结构 - 特性关系的数据库； 3） 深入了解优化的树突向量的设计。这些研究还将提供详细的 有关这类新型树突的两亲及其的物理化学和生物学信息 相应的组件，这是功能性树枝状聚合物/DNA组件的未来开发的关键 用于基因输送。 与公共卫生有关： 仍需要创新的治疗或治愈结肠癌的策略。今天，当前的治疗方案 导致患者护理的改善，但转移性结肠的缓解率仅保留约35％ 癌症患者。在此提案中，描述了新定义明确的聚合物以递送肿瘤 用于治疗结肠癌的抑制基因。

项目成果

Anionic amphiphilic dendrimers as antibacterial agents.

• DOI: 10.1021/ja806912a
• 发表时间: 2008-11-05
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Meyers, Steven R.;Juhn, Frank S.;Griset, Aaron P.;Luman, Nathanael R.;Grinstaff, Mark W.
• 通讯作者: Grinstaff, Mark W.