Advances in ß-Thalassemia: From Molecular Biology to Clinical Practice

Beta-thalassemia (ß-thalassemia) is an autosomal recessive disorder of haemoglobin inheritance resulting due to mutations of HBB gene present on chromosome 11 that lead to quantitative deficiency of ß-globin chains. The defect results in the accumulation of unpaired α-globin chains, inducing high rates of apoptosis in erythroid precursors, ineffective erythropoiesis, severe anaemia and progressive systemic iron overload. The conventional clinical approach is lifelong blood transfusion with regular iron chelation therapy but patients remain at risk of secondary organ toxicity. This review delineates the rapid paradigm shift in management of ß-thalassemia from conventional, supportive strategies toward personalised precision medicine. It discusses critical modern diagnostic methodologies, such as high- performance liquid chromatography (HPLC) and multiplex ligation-dependent probe amplification (MLPA), alongside pioneering therapeutic interventions. This paper reviews the clinical efficacy, regulatory milestones and mechanisms of action of the recently FDA-approved autologous hematopoietic stem cell gene therapies and CRISPR/Cas9-based gene-editing systems. It also discusses new targeted drug therapies and novel hepcidin-ferroportin axis modulators. It highlights important implementation challenges, including high costs of treatment, disparities in access across the world, and the integration of multi-omics data, and emphasizes the pathways needed to translate these advanced genomic innovations into accessible curative clinical standards on a global scale.