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

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个人。迫切需要一种安全、有效和易于应用的治疗方法来改善受损的伤口愈合。对于糖尿病患者来说，这种情况最紧迫，他们的足部溃疡是美国最常见的下肢截肢原因。该项目最初将导致一种治疗方式的营销，这种治疗方式将促进 糖尿病足溃疡的愈合。它将用于顽固性溃疡，在那里愈合没有进展。它也可以用于其他难于处理的伤口。目前还没有有效的治疗方法 在这个时候，这样的伤口。我们这项SBIR的目标是开发一种使用离子导入的新的强大的转基因策略。我们有初步工作表明，这可以是有效的。使用低电压进行离子导入，以在组织中产生电流。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阴极。在这项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，优化电极阵列和电气参数，以实现适合于改善伤口愈合的转染体。在第二阶段，我们将在猪模型中评估该方法的有效性和安全性。我们的研究小组已经证明，转录因子缺氧诱导因子-1(HIF-1)可以促进伤口愈合。像HIF-1这样的多肽的DNA传递是必要的，因为由于吸收差，简单地应用多肽生长因子并不有效，而且多肽在真皮中被多肽酶迅速破坏。DNA质粒传递促进了多肽在真皮中的持续产生，从而绕过了这些传递问题。

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.