Nanoscale Functional Dendrimer-DNA Assemblies

纳米级功能性树枝状聚合物-DNA 组装体

• 批准号: 7390402
• 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 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390402
• 关键词: Address; Affect; Architecture; Basic Science; Benchmarking; Binding; Biological; Biological Assay; Biology; Biomimetics; Cancer Patient; Cells; Characteristics; Charge; Chromosomes; Class; Classification; Cleaved cell; Colon Carcinoma; DNA; DNA Binding; DNA Packaging; Databases; 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; Modification; Molecular; NIH Program Announcements; Nanostructures; Nanotechnology; Non-Viral Vector; Nuclear; Numbers; Pathway interactions; Patient Care; Phosphorylation; Play; Polymers; Preparation; Process; Property; Protein p53; Proteins; Public Health; Range; Rate; Reaction; Reporter Genes; Research; Research Personnel; Role; Safety; Shapes; Structure; System; TP53 gene; Techniques; Today; Transfection; Transmission Electron Microscopy; Treatment Protocols; Tumor Suppressor Genes; Vaccines; Viral Vector; base; cancer cell; cancer therapy; colon cancer cell line; controlled release; cytotoxicity; design; esterase; gene therapy; improved; innovation; insight; interest; macromolecule; nanoscale; nanoscience; novel; novel strategies; programs; research clinical testing; response; size; 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.

该提案描述了由树突状细胞组成的新基因递送载体的制备和评价。 两亲物和DMA。这些新的功能性树枝状两亲物经历了从 通过酯酶催化的细胞内反应将阳离子转化为阴离子， 组装件.我们假设这种与DNA静电相互作用的变化将导致基因表达的增加。 转染水平。建议进行详细、系统的调查，包括以下三个具体方面： 这份为期三年的R21提案的目标是： 目标1.确定结合所需的树枝状两亲物的关键分子特征， 释放DNA 目标二。表征由树枝状两亲物形成的纳米级组装体， 两亲物和DNA。 目标3.树突状两亲物/DNA组装体与细胞的体外功能相互作用及其递送 p53基因转移到结肠癌细胞中。 成功完成这项研究的结果将是：1）一种或多种功能性树枝状两亲物， 将p53基因递送至结肠癌细胞; 2）结构-性质关系的数据库;以及3） 深入了解优化的树突状载体的设计。这些研究还将提供详细的 这类新的树枝状两亲物的物理化学和生物学信息及其 这是未来发展功能性树状聚合物/DNA组装体的关键 用于基因传递。 与公共卫生的相关性： 仍然需要治疗或治愈结肠癌的创新策略。今天，目前的治疗方案 已经改善了患者的护理，但对于转移性结肠癌， 癌症患者。在该提案中，描述了用于递送肿瘤的新的定义明确的聚合物 用于治疗结肠癌的抑制基因。