The general theme of Project 2 is improved therapy for Fanconi Anemia patients. In addition to the testing of novel non-viral gene transfer methods and the development of improved murine models, the role of telomere shortening in the evolution of clinical disease will be examined. The successful use of bone marrow transplantation in FA makes gene therapy directed at hematopoietic stem cellS (HSC) a viable approach for the treatment of hematological disease. Unforttmately, the stem cells of FA patients are both scarce and fragile, making standard gene therapy approaches difficult and establishing the need for alternate approaches. In addition, no interventions currently exist for the non-hematological manifestations of FA, particutarly solid tumors which occur late in the course of the disease. Improved murme models of FA now make it possible to test small molecules with the potential to delay cancer. Novel gene therapy methods will be tested in Aims l (Sleeping Beauty transposon) and 2 (phi C31 phage integrase).
Aim 3 will test multiple Compounds for their ability to prevent or delay tumors in FA knockout mice (cancer chemoprevention). Finally, Aim 4 is directed at improving murine models of FA and exploring the role of telomere shortening in the pathophysiology of FA.
Showing the most recent 10 out of 106 publications
