Shrestha, Archana et al. Molecular Therapy Methods & Clinical Development, Volume 33, Issue 2, 101439
This study is about a new gene therapy approach to treat sickle cell anemia (SCA). Scientists used a type of virus called a lentiviral vector (LV) to deliver a modified human γ-globin gene into blood stem cells.
A lentiviral vector is a delivery system. It carries a gene of interest—like the modified γ-globin gene in the sickle cell therapy—into the target cells, often stem cells, so those cells can start producing a desired protein.
This γ-globin gene makes fetal hemoglobin (HbF), which helps prevent the red blood cells from sickling. The researchers created two versions of the gene: One named GbGM, with a mutation to make more HbF, and the other GbGMI, which has a safety feature called an insulator to prevent unwanted activation of other genes.
In experiments with mice that have SCA, both versions successfully corrected the disease. The treated mice had more healthy red blood cells, less anemia, better blood flow, and improved survival compared to untreated mice. The therapy also worked in human blood stem cells transplanted into mice, where the cells continued to produce HbF without harmful side effects.
The study showed that the therapy is effective and appears safe, with minimal risk of activating cancer-related genes. Based on these strong preclinical results, the GbGM vector was chosen to move forward into human clinical trials as a potential long-term cure for sickle cell anemia.
