Topical Charge Driven DNA Delivery to the Skin

描述（由申请人提供）：本申请提出探索一种用于皮肤的新型DNA递送平台，其利用局部电荷作为活细胞摄取DNA的介体。这种新的物理DNA递送技术与其他方法不同，因为它不使用化学或生物制剂。它与其他物理DNA递送方法的不同之处在于，DNA被驱动到皮肤中并被递送到皮肤的活细胞，而不需要注射、侵入性程序或与任何设备的皮肤接触。初步研究表明，拟议的研究将取得成功。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作用，并确定获得生物学/临床相关反应是否可行。该研究旨在：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和皮肤中的任何不良组织学影响;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。 公共卫生相关性：这项研究与公共卫生有关，因为其结果可能导致成功的基于DNA的治疗方法，用于许多类型的疾病，这些疾病需要将治疗性蛋白质分泌到血液中。此外，它可能会导致一种更好的方法来应用DNA疫苗对抗传染病。

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.