Gene therapy treatment for severe anemia

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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.