Even after decades of research, Sickle cell anemia (SCA) still has limited treatment options. The recommended care is a palliative treatment based on frequent blood transfusions and medications to relieve the pain. The currently available cure for sickle cell anemia is bone marrow transplantation. However, with Gene editing, scientists have successfully identified different gene therapy applications that will be used as a curative treatment.
Gene editing therapy for Sickle cell anemia is here – and its research is advancing steadily. Genome editing technology, such as CRISPR/Cas9, has revolutionized SCA treatment. CRISPR gave the SCA research a new direction, and we now have multiple CRISPR-based treatments undergoing clinical trials.
CRISPR and Sickle Cell Therapy:
CRISPR involves three steps: collecting hematopoietic stem cells from the patients, modifying the collected cells in the lab, and infusion of the modified cells into the same patient from whom the cells were initially collected. This procedure is being seen as the potential cure for SCD.
It can be used on both adult as well as fetal Hb levels. For adult Hb, the approach is to repair the mutation in the gene responsible for sickle cell disease. First, CRISPR introduces a DNA break to the ß-globin gene. The break site then introduces a correction to the gene via homology-directed repair (HDR). This is also called a gene knock-in. The edited cells, which can now produce normal hemoglobin, are re-implanted/ infused in the patient's bloodstream.
For fetal hemoglobin (Hb F), CRISPR sickle cell gene therapy, commonly known as gene knockout, is used for fetal hemoglobin (Hb F). It involves switching off the gene that suppresses Hb F, which causes Hb F to be expressed, and the mutated adult Hb gets replaced.
Sickle Cell and CRISPR: On-going Human Trials
Clinical studies are going on to explore the safety and efficacy profile of CTX001. Scientists believe that CTX001 will become the first gene editing therapy that will be used globally by all SCA patients.
SCA has now become an ideal target for gene therapy. It is because; a single mutation causes the disease, and SCA treatment can also be used in treating Thalassemia. Consequently, the disease has become one of the most competitive fields in gene editing therapy. Apart from the therapies mentioned above, multiple other candidates are undergoing different phases of clinical trials, including: