Gene Therapy for Hemoglobinopathy Current Status and Future Direction

Management of symptomatic hemoglobinopathies, as exemplified by transfusion-dependent beta thalassemia (TDT), non-transfusion-dependent severe beta thalassemia (NTD), and sickle cell disease (SCD), have been evolving over the last seven decades, but unmet needs to manage this severe disease in the form of gene therapy remain. Success of allogenic stem cell transfusion in symptomatic haemoglobinopathies as a form of allogenic gene replacement therapy started in the 1980s, soon brought to the fore its limitations, e.g., limited applicability, morbidity, and mortality. Relapse back into the original condition after the procedure. However, the procedure produced long-term amelioration of the disease in a substantial number of patients on whom this therapy was applied. Gene replacement, gene correction, gene deletion, etc., as a therapeutic modality evolved over the last 35 years through the construction of better transgene, suitable vectors, improved collection techniques for autologous stem cells, and ex vivo gene therapy through successful animal model experimentation and careful clinical trials. These trials, which started from 2010, became successful and have now entered phase 3 of the program. However, a hurdle for gene therapy still remains. Quest for suitable means of providing in vivo gene therapy and non-chemo conditioning protocols is avidly sought after.