An article published earlier this year by Fierce Biotech outlines an approach that was developed by researchers at the Fred Hutchinson Cancer Research Center.
Using CRISPR-Cas9’s gene-editing method the researchers were able to increase fetal hemoglobin in animal models. This was accomplished by the introduction of a mutation, which is a change in the genetic material of a cell.
Fred Hutchinson’s study represents a first attempt at editing a subset of adult blood stem cells. These specialized cells are responsible for all the cells in the immune and blood system.
About Fetal Hemoglobin
Hereditary persistence of fetal hemoglobin (HPHF) is a benign condition whereby the production of fetal hemoglobin does not stop as it should shortly after birth but continues into adulthood.
The senior author of the Research Center’s study is Hans-Peter Kiem. Dr. Kiem and his team of researchers used CRISPR-Cas9 to extract a portion of genetic code that normally turns off fetal hemoglobin proteins. Snipping the control DNA resulted in a continuous flow of red blood cells producing higher levels of fetal hemoglobin.
CRISPR-Cas9 is a powerful tool that can cut portions of DNA precisely, thereby targeting and removing only unwanted genes.
Dr. Kiem’s team used stem cells with the CD90 antigen. The antigen is a diagnostic marker that induces an immune response and can regenerate the blood system. His method used in the animal model study is based on stem cells found in the patient’s bone marrow. These cells, called hematopoietic stem cells, produce red blood cells and hemoglobin that transports oxygen to all the tissues in the body.
The study resulted in long-lasting fetal hemoglobin that offset the defective adult hemoglobin.
About Sickle Cell Disease
Sickle cell disease is inherited from both parents. If the child inherits the sickle cell gene from only one parent, he or she will not have symptoms. It is considered a sickle cell trait, but not the disease.
Normal red blood cells are formed like a disk, but with sickle cell disease, they are shaped like a crescent or sickle and carry less oxygen though out the body.
About Hemoglobin S
Hemoglobin S is abnormal hemoglobin known to be the cause of sickle cell anemia. The abnormal crescent shape of the Hemoglobin S cells reduces the amount of oxygen throughout the body’s tissues.
The disease is most common in people of Mediterranean and African heritage. At a lesser degree, Sickle cell affects people in Central and South America and the Middle East.
And Now the Cost
Although the cost has been set at $1.75 million initially, the Fred Hutchinson team may be able to mitigate it somewhat by cutting the transplanted cells ten-fold.
Several companies such as CRISPR Therapeutics and Vertex are making their way to the forefront. Their CTX001 stem cell therapy was awarded Fast Track Designation to treat sickle cell disease.
Another company, Aruvant Sciences, is developing RVT-1801 gene therapy for beta thalassemia and sickle cell disease. The company announced positive data from its initial trial. RVT-1801’s technology increases red blood cells through the insertion of fetal hemoglobin genes into stem cells.
The scientific community is committed to improving CRISPR for blood disorders. Dr. Kiem and his team are now conducting long-term studies regarding safety profiles. He suggests that their success in editing cells in one group can be carried over to other conditions such as cancers and HIV.