Gene Therapy: Treatment of Sickle Cell Disease
‘Gene therapy is “the use of genes as medicine”. It involves the transfer of a working gene copy into specific cells of an individual in order to repair a faulty gene copy 1 .’ Since the 1980s, it has been emerging as a promising new technology which aims to treat and prevent many diseases and disorders, and in particular, those which are hereditary. In previous years, its potential and success in treating genetic disorders has rendered it one of the most prevalent and encouraging approaches in the field of genetics 2-5 . ‘If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein 6 .’ In the treatment of diseases, gene therapy usually involves the use of viral vectors that act as carriers. Primarily, a corrected gene is inserted into a viral vector. Typically, that viral vector is genetically modified so that it infects the targeted cells to deliver the new gene, without causing disease to the cells and tissues inside the body. Once a faulty gene is identified, the viral vector is used to deliver a duplication of the correctly functioning gene to the targeted cells 6 . When the gene reaches the cells, transcription takes place in which specialized proteins make a copy of the DNA sequence in the gene in the form of messenger RNA. mRNA then transfers this genetic sequence outside the nucleus. Ultimately, translation takes place, and this is the phase in which the cell machinery reads the genetic sequence or instructions and synthesizes the desired proteins 7 .
Sickle cell disease is a disorder that results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. The use of gene therapy in patients with this disorder is complicated. This is due to complex cellular abnormalities and challenges that may hurdle achieving effective and persistent inhibition of polymerization of hemoglobin S. This report describes a trial where a patient was treated with lentiviral vector–mediated addition of an anti-sickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning, but none were observed with the lentiviral vector. Fifteen months after treatment, the level of therapeutic anti-sickling β-globin remained high (approximately 50% of β-like–globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease.