Stem cell gene editing is a promising new method for treating sickle cell disease

Bioengineers from Rice University, US, have successfully used gene editing technology to correct mutations in stem cells derived from the peripheral blood of patients with sickle cell disease. The results of the study were presented at the annual meeting of the American Association for the Advancement of Science (AAAS) in 2018 in Austin, Texas.

Sickle cell disease is the most severe form of hemoglobinopathies, which characterized by a violation of the formation of normal hemoglobin chains in erythrocytes, caused by a genetic mutation.

As a result, an abnormal hemoglobin is formed, and the erythrocytes are stretched, acquiring a shape resembling a sickle (hence the name of the disease). Deformed erythrocytes are rapidly destroyed, clogged blood vessels, causing many complications and even death.

In this study, a group of scientists from the University of Rice, Baylor College of Medicine, Texas Children’s Hospital and Stanford University developed a cure for this hereditary disease.

“Sickle cell disease is caused by a single mutation in the beta-globin gene (in the stem cell’s DNA)”, – said Gang Bao, PhD, a member of the research team and a bioengineer at Rice. “The idea is to correct that particular mutation, and then stem cells that have the correction would differentiate into normal blood cells, including red blood cells. Those will then be healthy blood cells.”

Researchers selected stem cells and hematopoietic progenitor cells with a specific cellular marker CD34. The cells were then changed using the CRISPR/Cas9 genome editing technology and a custom DNA template to fix the mutation.

Scientists injected these altered cells into the bone marrow of immunodeficient mice and observed how many retained the edit after 19 weeks.

The results showed that their level remained stable all this time. However, the researchers also found that in addition to small mutations or deletions, the CRISPR/Cas9 system could introduce large alterations to the genes in patients’ cells. These off-target effects could cause a disease.

The data obtained from the research opens a new way in the treatment of sickle-cell anemia, scientists believe. Obstacles in the way of a cure include optimizing the CRISPR/Cas9 system to eliminate off-target effects, as well as finding a way to further increase the amount of gene-corrected stem cells.

Bao pointed out that the researchers still don’t know whether the number of reconstituted cells is sufficient (20 to 40%) for the complete recovery of the patient.

“We’d like to say, “Yes”, but we don’t really know yet. That’s something we hope to learn from an eventual clinical trial.”