A NOVEL ELECTROPORATION SYSTEM FOR GENE THERAPY WITH EPO

我们建议使用专有的TriGrid电穿孔系统（TES）来递送和延长促红细胞生成素（EPO）的表达。重组形式的EPO在商业上可用于治疗与HIV治疗和化疗引起的骨髓衰竭相关的贫血，以及慢性肾衰竭。然而，这种治疗平均每周必须进行三次。其他人已经描述了通过简单的针电极将EPO电穿孔到小鼠肌肉组织中可以有效地提高血液中EPO和红细胞压积的水平长达6个月，这表明作为标准EPO治疗的替代方案的潜在可行性。我们建议证明TES将报告基因和促红细胞生成素递送到肌肉组织的可行性，以及TES比目前的促红细胞生成素递送模式具有的优势，特别是在促红细胞生成素的持续表达方面。我们期望TES在EPO输送中的发展将为目前接受EPO治疗的患者提供更方便和更便宜的治疗。TES的未来可能不仅仅是为替代疗法提供基因，而且还可以为HIV和癌症治疗提供DNA疫苗来刺激宿主免疫反应。拟议的商业应用：epgen是一种由Amgen制药公司生产的人促红细胞生成素（EPO）的重组形式，估计每年的销售额超过5亿美元。一种治疗方法的发展是非常诱人的，这种治疗方法可以让身体制造自己的促红细胞生成素（EPO）来刺激红细胞的产生，作为对疾病治疗引起的贫血的反应。通过使用Ichor的电穿孔阵列在肌肉中引入和表达EPO基因，人体将能够在更长的时间内产生内源性EPO，并减少患者治疗贫血所需的治疗次数，从而降低总体治疗成本。对艾滋病和癌症患者的护理成本已经很高，这往往使这种改善其生活质量的治疗变得负担不起。

We propose to use a proprietary TriGrid Electroporation System (TES) for the delivery and prolonged expression of erythropoietin (EPO). Recombinant forms of EPO are commercially available as treatment for anemias associated with bone marrow depletion from HIV treatment and chemotherapy, and chronic renal failure. However, on average, this treatment must be delivered three times a week. Electroporation of EPO into mouse muscle tissue by simple needle electrodes has been described by others to be effective in increasing the level of EPO and hematocrit in blood for up to 6 months, suggesting potential viability as an alternative to standard EPO therapies. We propose to demonstrate feasibility of TES in delivering a reporter gene and EPO into muscle tissue and the advantages TES has over current modes of EPO delivery, particularly in the sustained expression of EPO to stimulate red blood cell production. We expect the development of TES in the delivery of EPO will provide a more convenient and less expensive treatment for patients undergoing current EPO therapy. The future of TES may not only be for the delivery of genes for replacement therapy, but also to deliver DNA vaccines to stimulate host immune responses for HIV and cancer treatment. PROPOSED COMMERCIAL APPLICATIONS: The estimated sales of Epogen, a human recombinant form of erythropoietin (EPO) manufactured by Amgen Pharmaceuticals, are above $500 million annually. The development of a treatment which allows the body to manufacture its own erythropoietin (EPO) to stimulate red blood cell production as a response to anemia caused by disease therapy, is very enticing. By introducing and expressing the EPO gene in muscle using Ichor's electroporation array, the body would be able to produce endogenous EPO for a more extended amount of time and would decrease the number of treatments patients would require to treat their anemia, thus decrease the overall cost of treatment. The already high cost of care for AIDS and cancer patients often makes this treatment to improve their quality of life unaffordable.