901. Transactivation of Fetal Hemoglobin Genes by Engineered Zinc-Finger Protein Transcription Factors for the Treatment of Sickle Cell Disease

Sickle cell disease (SCD) is caused by a single mutation in the adult beta-globin gene that drastically reduces the solubility of deoxygenated hemoglobin, leading to chronic hemolytic anemia. Despite the degree of molecular understanding regarding the cause of this disease, there is still no adequate long-term treatment. To address this unmet need, we are developing a novel therapeutic approach to SCD, which employs engineered zinc-finger protein transcription factors (ZFP TFs). ZFP TFs can be designed to regulate the expression of any endogenous gene. In this regard, it is well established that the clinical consequences of the sickle mutation in the adult beta-globin gene can be alleviated by overexpression of the fetal gamma-globin or the minor adult delta-globin gene. ZFP TF activators of gamma or delta globin thus represent a potential therapeutic intervention in SCD.