BEYOND GENE THERAPY: EXPERIMENTAL PERSPECTIVES OF GENE THERAPY IN HEMOGLOBINOPATHIES

β-hemoglobinopathies are caused by mutations affecting adult hemoglobin β-chain production. The only curative treatment is allogenic hematopoietic stem/progenitor cells (HSPCs) transplantation, an approach limited by compatible donor availability and immunological complications. Therefore, transplantation of autologous, genetically modified HSPCs is an attractive therapeutic option. However, current gene therapy strategies based on the use of lentiviral vectors or CRISPR/Cas9 nuclease are not equally effective in all the patients and/or raise safety concerns. Base, prime and epigenome editing are novel, promising CRISPR/Cas9-based genome editing technologies that allow the introduction of mutations in the DNA generating few or no dangerous double strand breaks. We will discuss the different genome editing strategies aiming either to correct the genetic defect or target disease modifiers in patient cells and provide a safe and effective treatment for β-hemoglobinopathies.