Development of inhibitors of RIOK3 for sickle cell anemia

National Center For Advancing Translational Sciences

Investigators

Abstract

Traditionally, beta-globinopathies such as sickle-cell anemia are treated through bone marrow transplantation. However, this method is limited due to high treatment costs and finding a matched-donor. This relies on increasing fetal hemoglobin to potentially cure the disease. The Tisdale Laboratory identified a protein called Rio-Kinase 3 (RIOK3) that inhibits the production of fetal hemoglobin. Inhibition of RIOK3 increases the production of fetal hemoglobin, suggesting that RIOK3 may be a promising novel therapeutic target to increase fetal hemoglobin expression. This project aims to use biophysical assays to identify a molecule capable of binding to RIOK3 to modulate its activity. During this reporting period, the collaborative team worked to develop an expression protocol to produce full length RIOK3, and additional work is underway to express the RIOK3 kinase domain to enable future high-throughput screening work.