A Novel Electroporation System for Gene Therapy with EPO

用于 EPO 基因治疗的新型电穿孔系统

• 批准号: 6527563
• 负责人: MAIDA M DE LAS ALAS
• 金额: $ 50.18万
• 依托单位: ICHOR MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-11 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527563
• 关键词: beta galactosidase; biomarker; biomedical equipment development; blood cell count; electroporation; erythropoietin; gene delivery system; gene expression; gene targeting; gene therapy; intramuscular injections; laboratory mouse; laboratory rat; miniature swine; reporter genes; striated muscles; technology /technique development; transfection /expression vector

(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.

（申请人提供）：我们建议开发一种临床 非病毒疗法治疗艾滋病/艾滋病毒和化疗引起的贫血 使用专有的 TriGrid 电穿孔系统 (EPT) 的患者。贫血是 目前通过重复施用重组促红细胞生成素进行治疗 （EPO），由于价格昂贵且这些患者不易获得 原发疾病的治疗费用已经很高。然而， 纠正这种贫血不仅可以改善生活质量，还可以 有潜力提高这些患者的生存概率。因此， 开发一种更具成本效益且同样有效的 EPO 方法 诸如 EPT 递送 Epo 质粒之类的疗法显然是合理的。Ichor 的 第一阶段的工作已经证明了递送含有以下物质的 DNA 质粒的可行性： 促红细胞生成素 (Epo) 等基因转化为小骨骼肌和大骨骼肌 啮齿类动物使用 EPT。第二阶段工作将涉及全面的剂量反应 治疗毒性和载体的分析和表征 生物分布。使用临床相关的质粒构建体，初始 实验将包括在正常和患病的啮齿动物模型中进行测试 评估生物反应并确定疗效和剂量。大型动物 将进行研究以验证剂量扩大并确定潜在毒性 以及与治疗相关的安全问题。 拟议的商业应用： Epogen 和 Procrit 的估计销售额，重组形式的促红细胞生成素 (EPO)， 每年超过20亿美元。 开发一种治疗方法，使身体能够 制造自己的 EPO 以刺激红细胞生成以响应治疗 - 诱发贫血，非常诱人。 通过在肌肉中导入并表达EPO基因 使用Ichor的电穿孔技术，人体将能够产生EPO 更长的时间并且会显着减少治疗次数 患者需要治疗贫血，从而降低总体治疗费用。 艾滋病和癌症患者本来就很高的护理费用往往使这种治疗方法难以实现 提高他们的生活质量，也许还有他们的生存可能性，这是负担不起的。