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Team corrects SCD mutation with iPS cells


 

Induced pluripotent stem cells
Credit: James Thomson

Using induced pluripotent stem (iPS) cells, researchers have corrected the genetic alteration that causes sickle cell disease (SCD).

The corrected stem cells were coaxed in vitro into immature red blood cells that then turned on a normal version of the gene.

The researchers caution that the work is years away from clinical use in patients, but it should provide tools for developing gene therapies for SCD and a variety of other hematologic disorders.

“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,” said lead study author Linzhao Cheng, PhD, of The Johns Hopkins School of Medicine.

Using an adult patient at The Johns Hopkins Hospital as their first case, the researchers isolated the patient’s bone marrow cells. After generating iPS cells from the bone marrow, the team put a normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.

The researchers sequenced the DNA from 300 different samples of iPS cells to identify those that contained correct copies of the hemoglobin gene and found 4. Three of these iPS cell lines didn’t pass muster in subsequent tests.

“The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells,” Dr Cheng said.

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,” Dr Cheng said. “We next have to learn how to properly convert these cells into mature red blood cells.”

This research was recently published online in Blood.

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