The long-term objectives of this project are l) to provide a cellular method of delivering constant levels of human thromboipoietin (huTPO) for sustained periods of time for patients with platelet deficiency due to chemotherapy and 2) to identify novel target genes induced by TPO in megakaryocytic precursors.
The specific aims are to i) transfect myoblast lines with expression vectors containing the huTPO gene and demonstrate secretion of huTPO in vitro; 2) transduce primary myoblasts with retroviral vectors containing huTPO; 3) demonstrate secretion of huTPO in vivo following myoblast transplantation into the skeletal muscles of syngeneic rodents or nude mice; 4) demonstrate that transplanted muscle cells secreting huTPO correct thrombocytopenia in a rodent model of chemotherapy-induced thrombocytopenia; and 5) use differential mRNA display to identify megakaryocyte genes targeted by TPO.
| Medina-Kauwe, L K; Kasahara, N; Kedes, L (2001) 3PO, a novel nonviral gene delivery system using engineered Ad5 penton proteins. Gene Ther 8:795-803 |
| Medina-Kauwe, L K; Maguire, M; Kasahara, N et al. (2001) Nonviral gene delivery to human breast cancer cells by targeted Ad5 penton proteins. Gene Ther 8:1753-61 |
| Medina-Kauwe, L K; Leung, V; Wu, L et al. (2000) Assessing the binding and endocytosis activity of cellular receptors using GFP-ligand fusions. Biotechniques 29:602-4, 606-8, 609 |
