Sickle cell anemia and homozygous beta thalassemia are diseases that both result from dysfunction of the beta globin gene. Patients with these disorders face few treatment options, suffer from episodes of severe pain, and often have shortened life expectancy. Reactivation of the developmentally silenced gamma globin gene can help ameliorate these symptoms. The long-term objective of this application is the production of a novel peptide inducer of gamma globin for therapeutic use. The experimental approach is to use human erythroleukemic cells for the in vivo selection of peptides that upregulate gamma globin expression. K562 cells will be transfected with expression vectors encoding random peptide sequences carried on a scaffold protein. Three targeting vectors will be used to deliver activatory peptides to nuclear targets, cytoplasmic signal transduction pathways, or cellular receptors. This novel approach allows the screening of millions of synthetic amino acid combinations with potential functions that have not undergone selection during the evolutionary process. The added power of this approach is its in vivo nature: it allows the isolation of peptides in a live-cell biological context that incorporates intracellular events such as folding or post translational modifications. PROPOSED COMMERCIAL APPLICATIONS: The identification of peptides that reactivate gamma globin expression will allow a new approach in the development of therapies for the beta chain hemoglobinopathies. New treatment options for sickle cell anemia and beta thalassemia would be welcome in the clinic, and would be of significant commercial value.