Individuals with severe sickle cell disease, who are between 18 and 50 years old, may be able to participate. A number of screening tests will be done to determine if subjects can participate. These include review of your past medical history, physical exam, blood and urine tests, pregnancy test, heart ultrasound, electrocardiogram, pulmonary function test, kidney function test, questionnaires, and magnetic resonance imaging (MRI) of the heart and liver. If eligible, blood stem cells will be collected by apheresis. A gene in these stem cells will then be edited to help the stem cells make more fetal hemoglobin. Higher levels of fetal hemoglobin can improve red blood cell sickling. You will then be hospitalized and chemotherapy will be given to empty out the bone marrow. The stem cells, with the modified gene, will then be given back to you. You will be followed for side effects and to see if the modified gene helps you make healthy red blood cells.