Repair sickle cell gene with stem cells

JOHNS HOPKINS (US) — Researchers have used a patient’s stem cells to correct the genetic alteration that causes sickle cell disease.

The painful, disabling inherited blood disorder affects mostly African-Americans.


In a test tube, the corrected stem cells were coaxed into becoming immature red blood cells that then turned on a normal version of the gene.

The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for sickle cell disease, or SCD, and a variety of other blood disorders.

In an article published recently in the journal Blood, researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD.

The disease is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. In people who inherit two copies—one from each parent—of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage, and premature death.

Although there are drugs and painkillers that control SCD symptoms, the only known cure—achieved rarely—has been bone marrow transplant. But because the vast majority of SCD patients are African-American and few African-Americans have registered in the bone marrow registry, it has been difficult to find compatible donors, says Linzhao Cheng, a professor of medicine at Johns Hopkins University.

“We’re now one step closer to developing a combination cell and gene therapy method that will allow us to use patients’ own cells to treat them.”

Using one adult patient as their first case, the researchers first isolated the patient’s bone marrow cells. After generating induced pluripotent stem (iPS) cells—adult cells that have been reprogrammed to behave like embryonic stem cells—from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.

In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels.

“We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene,” explains Cheng. “We next have to learn how to properly convert these cells into mature red blood cells.”

The research was funded by grants from the Maryland Stem Cell Fund and the National Institutes of Health, and by a fellowship from the Siebel Foundation.

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