Gene therapy treatment for severe anemia

基因疗法治疗严重贫血

• 批准号: 7095281
• 负责人: MAGDOLNA G SEBESTYEN
• 金额: $ 24.07万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095281
• 关键词: Macaca mulatta; anemia; chronic renal failure; erythropoietin; gene delivery system; gene expression; gene therapy; genetic promoter element; laboratory rat; nonhuman therapy evaluation; plasmids; technology /technique development; therapy design /development; transfection

DESCRIPTION (provided by applicant): Gene therapy holds promise for the treatment of both acquired and genetic disorders. Patients with diseases such as end-stage kidney disease, acquired immunodeficiency syndrome and cancer often develop anemia that can be treated by the frequent injection of recombinant human erythropoietin (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 also be produced at ectopic sites and secreted to the serum. We have shown that delivering the EPO gene to skeletal muscle can alleviate anemia in an animal model. We also discovered that a novel method of a minimally invasive intravascular delivery of naked plasmid DNA, results in highly efficient transfection of skeletal muscle. This Phase II project will use this simple and safe gene delivery approach and will combine it with an innovative way to control EPO expression in order to develop a regulatable gene therapy protocol for the treatment of severe anemia.

描述（由申请人提供）：基因治疗有望治疗获得性和遗传性疾病。患有终末期肾病、获得性免疫缺陷综合征和癌症等疾病的患者通常会出现贫血，这种贫血可以通过频繁注射重组人促红细胞生成素（EPO）蛋白来治疗。通过基因疗法递送EPO将提供显著的治疗益处。EPO通常在肾脏中表达，由于严重的器官衰竭，肾脏是大多数患者基因治疗的不良靶点。然而，血清蛋白如EPO也可以在异位部位产生并分泌到血清中。我们已经证明，在动物模型中，将EPO基因传递到骨骼肌可以缓解贫血。我们还发现，一种新的方法，一个最低限度的侵入性血管内输送裸质粒DNA，结果在骨骼肌的高效转染。该II期项目将使用这种简单安全的基因递送方法，并将其与控制EPO表达的创新方法相结合，以开发用于治疗严重贫血的可调控基因治疗方案。

项目成果

Progress toward a nonviral gene therapy protocol for the treatment of anemia.

• DOI: 10.1089/hum.2006.186
• 发表时间: 2007-04
• 期刊: Human gene therapy
• 影响因子: 4.2
• 作者: M. G. Sebestyén;J. Hegge;M. Noble;D. Lewis;H. Herweijer;J. Wolff