Comparative Analysis of Genome Editing for Curing Sickle Cell Disease: Induction of Fetal Hemoglobin and Gene Correction of Sickle Gene

Abstract

Known as a monogenic disease, Sickle Cell Disease (SCD) is a collective term for a series of red blood cell disorders affecting a large population in the world. Though current treatments exist and are proven effective (i.e., bone marrow transplant), accessibility severely limits their impact on most patients. Because the monogenic nature of SCD renders it simple to study, scientists are currently attempting to use gene therapy and genome editing to cure the disease. The genome editing approaches are mainly comprised of two methods: reactivating the previously suppressed fetal hemoglobin or a direct gene correction at the mutated residue in the adult beta (β) globin gene. Each approach is supported by a handful of in vitro experiments demonstrating sufficient levels of fetal hemoglobin activation or production of correct β globin in edited cells to rescue SCD. Although genome editing has shown great potential to treat this deadly disease, there remains much more work in in vivo and clinical trials to be done for further long-term evaluation before these approaches to be approved for use in humans. Safety issues and the long-term effects of the genome editing reagents are key topics that require large efforts to improve upon.