Topical Charge Driven DNA Delivery to the Skin

局部电荷驱动 DNA 递送至皮肤

• 批准号: 7978722
• 负责人: Mark J. Jaroszeski
• 金额: $ 18.38万
• 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: 2010-07-05 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7978722
• 关键词: Biological; Biological Assay; Biological Models; Biological Products; Blood; Cavia; Cells; Characteristics; Charge; Chemicals; Clinical; Communicable Diseases; Comparative Study; DNA; DNA Vaccines; DNA delivery; Data; Devices; Disease; Dose; Electrodes; Electroporation; Erythropoietin; Fluorescence; Fluorescence Microscopy; Generations; Genes; Goals; HIV Antigens; HIV Envelope Protein gp120; Histologic; Injection of therapeutic agent; Ions; Kinetics; Lead; Life; Location; Luciferases; Mediating; Mediator of activation protein; Methods; Modeling; Molecular; Mus; Muscle; Pain; Plasmids; Procedures; Process; Protein Secretion; Proteins; Public Health; Reporter; Research; Skin; Surface; System; Technology; Therapeutic; Tissues; Topical application; Vaccination; Vaccine Antigen; base; cell type; clinically relevant; design; driving force; gene gun; in vivo; intradermal injection; new technology; novel; plasmid DNA; programs; public health relevance; red fluorescent protein; response; therapeutic protein; therapeutic vaccine; uptake

DESCRIPTION (provided by applicant): This application proposes to explore a novel DNA delivery platform for skin that utilizes topical electrical charge as a mediator of DNA uptake by living cells. This new physical DNA delivery technology differs from other methods in that it does not utilize chemical or biological agents. It differs from other physical DNA delivery methods in that DNA is driven into the skin and delivered to living cells of the skin without the need for an injection, invasive procedures, or skin contact with any device. Preliminary studies indicate that the proposed study will be successful. The overall goal of this R21 study is to characterize and ultimately maximize the effects of topical charge mediated DNA delivery to cells within the skin and to determine if it is feasible to obtain responses that are biologically/clinically relevant. The study aims are designed to: investigate the translocation of plasmid DNA through the skin; determine the effects of charge dose and DNA dose on expression; identify the location of expressing cells and any adverse histological effects in the skin; determine the feasibility of using this technology for vaccination with DNA, and evaluate the potential of this delivery method for inducing therapeutic protein secretion. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to successful DNA based 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）：本申请旨在探索一种新型皮肤 DNA 递送平台，该平台利用局部电荷作为活细胞摄取 DNA 的介质。这种新的物理 DNA 传递技术与其他方法的不同之处在于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，DNA 被驱动到皮肤中并传递到皮肤的活细胞，而不需要注射、侵入性操作或皮肤与任何设备接触。初步研究表明拟议的研究将会成功。这项 R21 研究的总体目标是表征并最终最大化局部电荷介导的 DNA 递送至皮肤内细胞的效果，并确定是否可以获得生物学/临床相关的反应。该研究的目的是：研究质粒 DNA 通过皮肤的易位；确定电荷剂量和DNA剂量对表达的影响；确定表达细胞的位置以及皮肤中任何不利的组织学影响；确定使用该技术进行 DNA 疫苗接种的可行性，并评估该递送方法诱导治疗性蛋白质分泌的潜力。 公共健康相关性：这项研究与公共健康相关，因为其结果可能会导致成功的基于 DNA 的治疗方法，用于治疗需要将治疗蛋白分泌到血液中的多种类型的疾病。此外，它可能会带来更好的方法来应用DNA疫苗来对抗传染病。