The potential use of miRNA technology in thalassemia therapy Lantip Rujito, Tirta Wardana
Faculty of Medicine, Universitas Jenderal Soedirman
Abstract
Thalassemias encompass a group of inherited hemoglobin disorders characterized by reduced or absent production of the α-- or β--globin chains, leading to anemia and other complications. Current management relies on lifelong blood transfusions and iron chelation, which is burdensome for patients. This review summarizes the emerging therapeutic potential of modulating microRNAs (miRNAs) to treat thalassemia. miRNAs are small non-coding RNAs that negatively regulate gene expression through sequence-specific binding to messenger RNAs. Many miRNAs are now recognized as critical regulators of erythropoiesis and are abnormally expressed in β--thalassemia. Therapeutically restoring levels of deficient miRNAs or inhibiting overexpression through miRNA mimics or inhibitors/antimiRs, respectively, has shown preclinical efficacy in ameliorating thalassemic phenotypes. The miR-144/451 cluster is especially compelling for targeted upregulation to reactivate fetal hemoglobin synthesis. Advances in delivery systems are addressing previous challenges in stability and targeting of miRNA-based drugs. While still early, gene therapy studies suggest combinatorial approaches with miRNA modulation may provide synergistic benefits. Several key considerations remain including enhancing delivery, minimizing off-target effects, and demonstrating long-term safety and efficacy. While no miRNA therapies have yet progressed to clinical testing for thalassemia specifically, important lessons are being learned through trials for other indications. If limitations can be overcome through multi-disciplinary collaboration, miRNAs hold great promise to expand and transform treatment options for thalassemia in the future by precisely targeting pathogenic molecular networks. Ongoing innovation continues to drive progress in this emerging field towards realizing the clinical potential of miRNA-based medicines for thalassemia patients
