Development of Streamed Ion Deposition for Efficient Plasmid DNA Delivery

用于高效质粒 DNA 递送的流式离子沉积的开发

• 批准号: 7790162
• 负责人: Mark J. Jaroszeski
• 金额: $ 20.88万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-05 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7790162
• 关键词: Animals; Antigens; Biological; Biological Assay; Biological Models; Biological Products; Blood; Cavia; Cells; Charge; Chemicals; Code; Communicable Diseases; Control Animal; Coupled; DNA; DNA Vaccines; DNA delivery; Data; Deposition; Development; Devices; Disease; Dose; Effectiveness; Electrodes; Electroporation; Erythropoietin; Gases; Gene Delivery; Generations; Goals; Hepatitis B Surface Antigens; Histologic; In Vitro; Investigation; Ions; Lead; Liquid substance; Location; Luciferases; Measurement; Mediating; Methodology; Methods; Modeling; Mus; Muscle; Muscle Contraction; Necrosis; Pain; Plasma; Plasmids; Prophylactic treatment; Proteins; Protocols documentation; Public Health; Publishing; Relative (related person); Reporter; Reporter Genes; Research; Sampling; Skin; Smooth Muscle; Stream; Surface; Technology; Testing; Therapeutic; Therapeutic Uses; Tissues; Vaccine Antigen; base; comparative; design; driving force; gene gun; gene therapy; in vivo; method development; novel; plasmid DNA; programs; prophylactic; public health relevance; red fluorescent protein; response; therapeutic protein; uptake; voltage

DESCRIPTION (provided by applicant): This application proposes to explore a novel DNA delivery platform for skin that utilizes a stream of ions generated in plasma (charged gas stream) to facilitate the uptake of DNA. This new physical DNA delivery technology differs from other technologies in that it does not utilize chemical or biological agents. It also differs from other physical DNA delivery methods in that it does not require contact between any devices and the skin; therefore, it is noninvasive. Preliminary studies have shown that it is possible to deliver foreign molecules to cells in vitro and plasmid DNA to normal mouse skin in vivo without the adverse stimulation noted when other electrical methodologies are used. Based on these findings, the hypothesis of this proposal is that streamed ion deposition can be used for efficient DNA delivery to skin. This hypothesis will be tested by performing specific aims that characterize its capacity to deliver plasmids encoding reporter molecules. It will also be tested with respect to delivering plasmid encoding an antigen and a secreted protein to explore the methods capacity for prophylactic and therapeutic use. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to treatments for many types of diseases that require the secretion of a therapeutic protein into the blood. In addition, it may lead to a better means of applying DNA vaccines against infectious diseases.

描述（由申请人提供）：本申请提出探索一种新的皮肤DNA递送平台，该平台利用等离子体（带电气流）中产生的离子流来促进DNA的吸收。这种新的物理DNA传递技术不同于其他技术，因为它不使用化学或生物制剂。它与其他物理DNA传递方法的不同之处在于，它不需要任何设备与皮肤接触；因此，它是非侵入性的。初步研究表明，可以在体外将外来分子输送到细胞中，并在体内将质粒DNA输送到正常小鼠的皮肤中，而不会出现其他电方法使用时出现的不良刺激。基于这些发现，本提案的假设是，离子流沉积可用于有效的DNA传递到皮肤。这一假设将通过执行特定目标来验证，该目标表征了其传递编码报告分子的质粒的能力。还将对该方法进行编码抗原和分泌蛋白的质粒递送测试，以探索该方法的预防和治疗能力。