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.

（由申请人提供）：我们建议开发临床 用于治疗诱导的艾滋病/HIV和化学疗法的治疗诱导贫血的非病毒疗法 使用专有Trigrid电穿孔系统（EPT）的患者。贫血是 目前通过重组红细胞生成素的重复给药治疗 （EPO），由于 原发性疾病的治疗成本已经提高。然而， 对这种贫血的纠正不仅会改善生活质量，还可以 有可能提高这些患者生存的可能性。因此， 开发更具成本效益和同样有效的EPO方法 显然是合理的，例如，EPO质粒的EPT递送等疗法。 第一阶段的工作表明了传递含有DNA质粒的可行性 诸如促红细胞生成素（EPO）之类的基因进入大小的骨骼肌肉 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 分析和处理毒性和载体的表征 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 评估生物学反应并建立功效和给药。大动物 将进行研究以验证剂量规模并确定潜在的毒性 和与治疗相关的安全问题。 拟议的商业应用： 估计的Epogen和procrit，重组形式的促红细胞生成素（EPO）的销售， 每年超过20亿美元。 治疗的发展，使身体得以 生产自己的EPO以响应治疗而刺激红细胞的产生 - 诱发的贫血，非常吸引人。 通过引入和表达肌肉中的EPO基因 使用Ichor的电穿孔技术，身体将能够为A的EPO生产 更长的时间，将大大减少治疗的数量 患者需要治疗贫血，从而降低治疗的整体成本。 艾滋病和癌症患者的已经很高的护理费用经常使这种治疗 提高他们的生活质量，也许是他们生存的可能性，无法承受。