Thalassemia is a disease affecting the red blood cells, prevalent in the Middle East and south Eastern Asia due to the prevalence of malaria. Currently, stem cell transplantation is the only curative treatment, which is limited by the availability of donor and compatibility of HLA. Other supportive treatment includes monthly transfusion and iron chelation only offers support but can have long term ill-effects such as alloimmunization and iron overload with organ malfunction. Here we will like to develop using the cutting edge gene editing CRISPR technology to develop a curative treatment. In this project, we will explore the chromosome accessibility and gene expression profile during erythropoiesis. This will help us to identify potential loci for gene editing and will perform in vitro and ex vivo assays to lay the groundwork as preclinical studies.