Genome Editing for β-Hemoglobinopathies: Advances and Challenges

beta-hemoglobinopathies are the most common genetic disorders worldwide and are caused by mutations affecting the production or the structure of adult hemoglobin. Patients affected by these diseases suffer from anemia, impaired oxygen delivery to tissues, and multi-organ damage. In the absence of a compatible donor for allogeneic bone marrow transplantation, the lifelong therapeutic options are symptomatic care, red blood cell transfusions and pharmacological treatments. The last decades of research established lentiviral-mediated gene therapy as an efficacious therapeutic strategy. However, this approach is highly expensive and associated with a variable outcome depending on the effectiveness of the viral vector and the quality of the cell product. In the last years, genome editing emerged as a valuable tool for the development of curative strategies for beta-hemoglobinopathies. Moreover, due to the wide range of its applications, genome editing has been extensively used to study regulatory mechanisms underlying globin gene regulation allowing the identification of novel genetic and pharmacological targets. In this work, we review the current advances and challenges of genome editing approaches to beta-hemoglobinopathies. Special focus has been directed towards strategies aimed at correcting the defective beta-globin gene or at inducing fetal hemoglobin (HbF), which are in an advanced state of clinical development.

Automated summary

Beta-hemoglobinopathies are genetic disorders caused by mutations affecting adult hemoglobin production or structure, leading to anemia and multi-organ damage. Current therapeutic options include symptomatic care, blood transfusions, and pharmacological treatments, with lentiviral-mediated gene therapy showing promise but being costly and variable in outcomes. Genome editing has emerged as a valuable tool for developing curative strategies for beta-hemoglobinopathies, with a focus on correcting defective beta-globin genes or inducing fetal hemoglobin production.