Sickle cell disease (SCD) results from a homozygous missense mutation in the β-globin gene that leads to polymerization of hemoglobin S. Its clinical manifestations can be critical with considerable morbidity and mortality. SCD can be treated using bone marrow transplantation, but is restricted to only those patients having an appropriately matched donor. Hence, gene therapy, involving the patient’s own cells, either by gene insertion or gene editing is a primary therapeutic option to cure SCD. However, only a few clinical trials have been performed with genetic therapy for treating SCD. In recent years, significant progress has been made in the area of gene therapy for treating monogenic hemoglobin disorders. Numerous therapies are currently in clinical trial stages or in preclinical stages. The safety and efficacy of gene therapy has been greatly improved with the initial use of γ-retrovirus vectors, followed by next-generation lentivirus vectors and latest gene editing techniques. Although the clinical interpretation of gene therapy has been successful, it involves certain limitations including complex cellular abnormalities, inadequate transgene expression and challenges in achieving effective and persistent inhibition of polymerization of hemoglobin S. This review intends to discuss gene therapy strategies specific to SCD, present state of the field and current status of the gene therapy clinical trials.
Dr. Salma AlDallal
Kuwait Ministry of Health, Amiri Hospital, Sharq, Kuwait.
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