Gene therapy treatment for severe anemia

描述（由申请人提供）：基因疗法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经常会出现贫血，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。通过基因疗法给药促生成素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，大多数患者的肾脏不是基因治疗的理想靶点。然而，血清蛋白如EPO也可以在异位位点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减轻贫血。我们还发现了一种微创血管内传递裸质粒DNA的新方法，可高效转染骨骼肌。该二期项目将使用这种简单安全的基因传递方法，并将其与一种控制EPO表达的创新方法相结合，以开发一种可调节的基因治疗方案，用于治疗严重贫血。

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.