Gene therapy treatment for severe anemia

基因疗法治疗严重贫血

• 批准号: 6443792
• 负责人: David Lawrence Lewis
• 金额: $ 10.29万
• 依托单位: MIRUS BIO CORPORATION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443792
• 关键词: anemia; chronic renal failure; erythropoietin; gene delivery system; gene expression; gene targeting; gene therapy; genetic promoter element; laboratory rat; plasmids; transfection

DESCRIPTION (provided by the applicant): Gene therapy holds a promise for the treatment of both acquired and genetic diseases. Patients with diseases including end-stage kidney disease, acquired immunodeficiency syndrome and patients who are treated for cancer with high dose chemotherapy and bone marrow transplantation often develop anemia that can be treated or prevented by injection of recombinant EPO protein. EPO delivery via gene therapy would provide a significant treatment benefit. EPO is normally expressed in the kidney, which is a poor target for gene therapy in most patients because of severe organ failure. Yet, serum proteins such as EPO can be produced at ectopic sites and secreted to the serum. A novel method of intra-vascular injection of plasmid DNA expression vector results in highly efficient tranfection of skeletal muscle. This project will use this simple and innovative approach to develop a gene therapy protocol for the treatment of severe anemia. In this Phase 1 application, experiments are proposed to optimize EPO expression following intra-vascular delivery of plasmid DNA expression vectors and test this gene therapy protocol in a severe anemia model. During the Phase II studies, intra-vascular delivery techniques will be optimized to target small, defined muscle groups in a safe clinically applicable protocol. PROPOSED COMMERCIAL APPLICATION: The intravascular delivery methodology will be used in Phase III for the internal development of gene therapy protocols for severe anemia and applications such as clotting factor abnormalities, phenylketonuria, a1-antitrypsin deficiency, complement factor deficiencies, and other hematologic or metabolic disorders within Mirus and licensed to other companies for use within their ene therapy applications.

描述（由申请人提供）：基因治疗有望实现 治疗获得性和遗传性疾病。患有疾病的患者 包括终末期肾病、获得性免疫缺陷综合征和 接受高剂量化疗和骨髓治疗的癌症患者 移植经常会出现贫血，可以通过以下方法治疗或预防 注射重组EPO蛋白。通过基因治疗输送 EPO 将 提供显着的治疗效益。 EPO 通常表达为 肾脏，对于大多数患者来说，这不是基因治疗的一个不良目标，因为 严重的器官衰竭。然而，血清蛋白如 EPO 可以在 异位点并分泌到血清中。一种新的血管内注射方法 注射质粒DNA表​​达载体可实现高效 骨骼肌的转染。这个项目将使用这个简单且 开发基因治疗方案的创新方法，用于治疗 严重贫血。在此第一阶段应用中，建议进行实验 血管内递送质粒 DNA 后优化 EPO 表达 表达载体并在严重贫血中测试该基因治疗方案 模型。在第二阶段研究期间，血管内输送技术将被 经过优化，以安全的临床方式针对小而明确的肌肉群 适用的协议。 拟议的商业应用： 血管内输送方法将用于第三阶段的内部开发 Mirus 内针对严重贫血和凝血因子异常、苯丙酮尿症、a1-抗胰蛋白酶缺乏、补体因子缺乏以及其他血液或代谢疾病等应用的基因治疗方案，并授权给其他公司在其烯治疗应用中使用。