A Novel Electroporation System for Gene Therapy with EPO

(申请人提供)：我们建议开发一种临床 艾滋病/艾滋病患者治疗性贫血的非病毒治疗与化疗 患者使用专有的TriGrid电穿孔系统(EPT)。贫血是 目前反复使用重组促红细胞生成素治疗 (EPO)，价格昂贵，这些患者不易获得，原因是 他们的原发病的治疗费用已经很高了。然而， 纠正这种贫血不仅将提高生活质量，而且还可能 有可能提高这些患者的生存概率。因此， 一种更经济有效的促红细胞生成素方法的开发 治疗，如EPT--运送EPO质粒，显然是合理的。 第一阶段的工作已经证明了传递含有以下物质的DNA质粒的可行性 促红细胞生成素(EPO)等基因进入大小骨骼肌 使用EPT的啮齿动物。第二阶段的工作将涉及全面的剂量反应 治疗毒性和病媒的分析和表征 生物分布。使用临床相关的质粒构建物，初始 实验将包括在正常和患病的啮齿动物模型上进行测试 评估生物反应，确定疗效和剂量。一种大型动物 将进行研究以验证剂量放大并确定潜在的毒性 以及与治疗相关的安全问题。 建议的商业应用： Epogen和Procrit，重组形式的促红细胞生成素(EPO)， 每年超过20亿美元。一种治疗方法的发展，使身体能够 制造自己的促红细胞生成素来刺激红细胞的产生以应对治疗- 诱发贫血，是非常诱人的。促红细胞生成素基因在肌肉中的导入和表达 使用Ichor的电穿孔技术，人体将能够为 更长的时间，并将显著减少治疗的数量 患者将需要治疗他们的贫血，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，这往往使这种治疗 提高他们的生活质量，也许他们生存的可能性是负担不起的。

(Provided by the applicant): We propose to develop a clinical non-viral therapy for treatment-induced anemia in AIDS/HIV and chemotherapy patients using a proprietary TriGrid electroporation system (EPT). Anemia is currently treated with repeated administration of recombinant erythropoietin (EPO), which is expensive and not readily available to these patients due to the already elevated cost of treatment for their primary disease. However, correction of this anemia will not only improve quality of life, but may also have the potential to improve these patients' probability of survival. Thus, development of a more cost effective and equally efficacious method of EPO therapy such as EPT-delivery of an Epo plasmid, is clearly justified.Ichor's Phase I work has shown the feasibility of delivering DNA plasmids containing genes such as erythropoietin (Epo), into skeletal muscle of small and large rodents using EPT. Phase II work will involve a comprehensive dose response analysis, and characterization of treatment toxicity and vector biodistribution. Using a clinically relevant plasmid construct, initial experiments will include testing in normal and diseased rodent models to evaluate biologic response and establish efficacy and dosing. A large animal study will be conducted to verify dose scale up and identify potential toxicity and safety issues associated with the therapy. PROPOSED COMMERCIAL APPLICATION: The estimated sales of Epogen and Procrit, recombinant forms of erythropoietin (EPO), are above $2 billion annually. The development of a treatment which allows the body to manufacture its own EPO to stimulate red blood cell production in response to treatment- induced anemia, is very enticiting. By introducing and expressing the EPO gene in muscle using Ichor's electroporation technology, the body would be able to produce EPO for a more extended amount of time and would significantly decrease the number of treatments patients would require to treat their anemia, thus decreasing 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 and perhaps their likelihood for survival, unaffordable.