Therapeutic Progress Using CRISPR-Cas9 Harbors Newfound Hope

Sickle cell anemia is the most widespread genetic disease in the world, and very prevalent in France where it affects one child for every 1900 births.

The name of this disease is derived from the “sickle” shaped appearance of the red blood cells caused by a defect in the cell’s hemoglobin. Hemoglobin is the main protein in the red blood cells which carries oxygen from the lungs to the tissues and helps eliminate carbon dioxide. In sickle cell anemia, the abnormal hemoglobin results in red blood cells that are fragile and rigid, leading to anemia, painful vaso-occlusive seizures and an increased risk of infection.

Sickle cell is an inherited genetic disease with recessive autosomal transmission, meaning that for a child to be affected by the disease, he must receive a mutated gene from each parent. A person with a single mutated allele is a non-symptomatic healthy carrier. If both parents are healthy carriers, there is a risk of one in four of having a child with sickle cell anemia. However, if one parent has sickle cell anemia and the other is a healthy carrier, the risk increases to one in two.

There are treatments available, and neonatal screening can result in a better management for those who are affected. Nonetheless, new research shows that genome modification using the CRISPR-Cas9 technique can treat the disease at the root cause, by repairing the defective gene where the red blood cells are formed.

In 2018, early experiments suggested that a clinical treatment for sickle cell using CRISPR-Cas9 appeared promising. Now the FDA (Food and Drug Administration) has given approval to scientists in San Francisco, Berkeley and Los Angeles (UCLA) to jointly collaborate on launching the first tests in humans based on CRISPR-Cas9 gene therapy. Using the patient’s own stem cells, these “genetic scissors” directly correct the mutation in the gene responsible for sickle cell anemia.

The procedure requires for some of the patient’s hematopoietic stem cells — the bone marrow cells that generate all the body’s red blood cells — to be harvested in order to undergo gene editing (with CRISPR-Cas9) outside the body. After these cells are removed, the remaining bone marrow is destroyed with chemotherapy. Finally, the CRISPR-modified or “correctly repaired” stem cells – are reinfused in the hope that they will develop and flourish in the bone marrow to generate normal red blood cells.

This harbors newfound hope for therapeutic progress using CRISPR-Cas9.

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