Gene Therapy in Sickle Cell Disease: Advanced Study

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.