A NOVEL ELECTROPORATION SYSTEM FOR GENE THERAPY WITH EPO

我们建议使用专利的TriGrid电穿孔系统(TES)来传递和延长红细胞生成素(EPO)的表达。重组形式的促红细胞生成素可用于治疗因艾滋病毒治疗和化疗导致的骨髓衰竭以及慢性肾功能衰竭所致的贫血。然而，平均而言，这种治疗必须每周提供三次。通过简单的针电极将EPO电穿孔到小鼠肌肉组织中，已经被其他人描述为有效地提高血液中EPO水平和红细胞压积长达6个月，这表明作为标准EPO疗法的替代方案具有潜在的可行性。我们建议证明TES将报告基因和EPO导入肌肉组织的可行性，以及TES相对于目前EPO输送方式的优势，特别是在持续表达EPO以刺激红细胞产生方面。我们预计，在EPO输送方面开发TES将为接受当前EPO治疗的患者提供更方便、更便宜的治疗方法。TES的未来可能不仅仅是提供替代疗法的基因，还可能提供DNA疫苗，以刺激宿主对艾滋病毒和癌症治疗的免疫反应。拟议的商业应用：Epogen是安进制药公司生产的一种人类重组形式的促红细胞生成素(EPO)，估计年销售额超过5亿美元。一种治疗方法的发展，允许身体产生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，这是非常诱人的。通过使用Ichor的电穿孔阵列在肌肉中导入和表达EPO基因，人体将能够在更长的时间内产生内源性EPO，并将减少患者治疗贫血所需的治疗次数，从而降低治疗的总体成本。艾滋病和癌症患者的护理费用已经很高，这往往使这种提高他们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.