Gene Therapy as the New Treatment for Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is one of the most common monogenic disorders in the world (۳۰۰,۰۰۰to ۴۰۰,۰۰۰ newborns per year). This disorder results from a point mutation in the β-globin gene. That causedabnormal hemoglobin production under hypoxic conditions. Autologous transplantation for β-globin genemodification using a lentiviral vector (LV) makes mutated gene modification possible. In this review, we discussβ and γ gene therapy in SCD.Methods: A literature search of PubMed and Google Scholar was conducted in the last two years. Articlesreporting gene therapy's effect on SCD patients and the methods of gene treatments were included. Studies werenarratively summarized in this review.Results: Gene therapy data for the treatment of sickle cell show improvement in hemoglobin (Hb) F level(increase the level of HbF), which immensely reduces the periods of sickling after treatment. Also, BCL ۱۱Agene editing with CRISPR-Cas۹ (clustered regularly interspaced short palindromic repeats–CRISPR-associatednuclease ۹) has shown that it is capable of decreasing HbS expression in patients compared to people with sicklecell traits. These results indicate that relieving the patient instead of treating it can be acceptable. However,considering that the data from clinical trials are preliminary, the long-term efficacy of gene therapy is stilldebatable.Conclusion: LV gene therapy is an effective and relatively safe therapy, but LV may have the risk of insertionalgenotoxicity. CRISPR-Cas۹ has only early clinical data. This approach may cause toxicity and increase the riskof translocations or loss of chromosomal arms. These methods need further development, but there will be newapproaches that hold promise for treatment