Development of Iontophoresis Device for Plasmid DNA Transfection of Hypoxia Inducible Factor-1 to Improve Wound Healing

开发用于缺氧诱导因子-1 的质粒 DNA 转染促进伤口愈合的离子电渗装置

基本信息

批准号：
8829949
负责人：
John W Harmon
金额：
$ 14.98万
依托单位：
CANTON BIOTECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-05 至 2016-09-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8829949
关键词：
Aging Amputation Animal Model Animals Anodes Area Biomedical Engineering Bipolar II Cathodes Characteristics Charge Clinic Clinical DNA DNA delivery Dermis Development Devices Diabetes Mellitus Diabetic Foot Ulcer Doctor of Philosophy Elderly Electrodes Electroporation Family suidae Foot Ulcer Funding Genetic Transcription Goals Growth Factor Healed Homing Image Impaired wound healing Individual Iontophoresis Lead Lower Extremity Marketing Messenger RNA Modality Modeling Modification Mus Peptide Hydrolases Peptides Pharmaceutical Preparations Phase Plasmid Cloning Vector Plasmids Play Production Role Safety Schools Small Business Innovation Research Grant Staging Stem cells Steroids Stromal Cell-Derived Factor 1 Time Tissues Transdermal substance administration Transfection Ulcer United States United States National Institutes of Health Universities Vascular Endothelial Growth Factors Work Wound Healing absorption aged design effective therapy healing high risk hypoxia inducible factor 1 improved innovation knockout animal novel novel strategies plasmid DNA prototype public health relevance transcription factor voltage wound

项目摘要

DESCRIPTION (provided by applicant): Impaired wound healing is an unfortunate consequence of diabetes. It is also seen in the elderly, as well as individuals taking steroid medication. There is an urgent need for a therapy that will be safe, effective, and easy to apply to improve impaired wound healing. The situation is most urgent for individuals with diabetes, whose foot ulcers are the most frequent cause for lower extremity amputations in the United States. This project will lead initially to the marketing of a treatment modality that will promote healing of diabetic foot ulcers. It will be used for recalcitrant ulcers where healing is not progressing. It can be used for other difficult wounds as well. There is no effective treatment for such wounds at this time. Our goal for this SBIR is to develop a novel robust transfection strategy using iontophoresis. We have preliminary work showing that this can be effective. Iontophoresis is performed using a low voltage to create an electrical current in tissue. In our situation the negatively charged plasmid DNA is driven through the tissue from the anode to the cathode. For Phase 1 of this SBIR we will work with a group from Johns Hopkins University, School of Bioengineering, to optimize the electrode arrays and electrical parameters to achieve transfection suitable for improving wound healing. In Phase 2 we will assess the efficacy and safety of the approach in a porcine model. Our group has shown that the transcription factor Hypoxia Inducible Factor- 1 (HIF-1) can improve wound healing. DNA delivery of a peptide like HIF- 1 is necessary because simple application of peptide growth factors has not been effective because of poor absorption, and because the peptides are rapidly destroyed by peptidases in the dermis. The DNA plasmid delivery promotes continuous production of the peptide in the dermis to circumvent these delivery problems.

描述（由申请人提供）：伤口愈合受损是糖尿病的一个不幸后果。它也见于老年人以及服用类固醇药物的人。迫切需要一种安全、有效且易于应用的疗法来改善受损的伤口愈合。对于糖尿病患者来说，情况最为紧迫，在美国，糖尿病患者的足部溃疡是导致下肢截肢的最常见原因。该项目最初将导致治疗方式的营销，从而促进治愈糖尿病足溃疡。它将用于治疗没有进展的顽固性溃疡。它也可用于其他困难的伤口。目前尚无有效治疗方法此时这样的伤口。我们此 SBIR 的目标是利用离子电渗疗法开发一种新颖的稳健转染策略。我们的初步工作表明这是有效的。离子电渗疗法是使用低电压在组织中产生电流来进行的。在我们的情况下，带负电荷的质粒 DNA 被驱动通过组织从阳极到达阴极。对于该 SBIR 的第一阶段，我们将与约翰霍普金斯大学生物工程学院的一个小组合作，优化电极阵列和电参数，以实现适合改善伤口愈合的转染。在第二阶段，我们将评估该方法在猪模型中的有效性和安全性。我们的研究小组已经证明转录因子缺氧诱导因子-1 (HIF-1) 可以改善伤口愈合。像 HIF-1 这样的肽的 DNA 递送是必要的，因为简单应用肽生长因子并不有效，因为吸收差，并且因为肽会被真皮中的肽酶迅速破坏。 DNA 质粒递送可促进真皮中肽的连续产生，从而避免这些递送问题。