Epigenetic editing: a promising alternative to genome editing for treating sickle cell disease and beta-thalassemia

Beta hemoglobinopathies, such as sickle cell anemia and beta thalassemia, are severe genetic diseases caused by defects in hemoglobin, the molecule that carries oxygen in the blood. These defects lead to chronic anemia and can cause serious damage to various organs. One “natural” way of compensating for this defect is the continued expression of fetal hemoglobin (HbF), a form normally present in the fetus and capable of making up for the faulty adult hemoglobin. Researchers at Institut Imagine are exploring innovative strategies for reactivating this HbF in patients. One is based on the genetic editing of blood stem cells, a promising approach which, however, still needs to be perfected in terms of safety. In parallel, the “Chromatin and gene regulation during development” team, headed by Annarita Miccio, is developing an epigenetic approach, which acts not on the DNA code, but on its regulators: chemical marks that control the activation or silencing of genes. By precisely modifying these marks, HbF expression can be revived without affecting the DNA itself. Simone Amistadi and Letizia Fontana's work, published in Nucleic Acid Research, shows that this method could offer a safe and effective alternative for treating these rare diseases, while enriching our understanding of the mechanisms that regulate gene expression.