Researchers from Innovative Genomics Initiative reveal potential to correct sickle cell mutation

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Frans Kuypers/Courtesy

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Thanks to CRISPR-Cas9 gene editing, which can manipulate the human genome, sickle cell disease is one step closer to a cure.

A study released by genetic researchers, including scientists with the Innovative Genomics Initiative, or IGI, at UC Berkeley, found that the researchers are able to potentially correct the sickle cell mutation —  mutated red blood cells — by genetically modifying stem cells that produce red blood cells in the bone marrow. The researchers first made a break in the stem cell and used a DNA molecule as a template to repair the break — then, when the modified stem cell produces red blood cells, it would no longer produce sickle cells.

“It is exciting to see CRISPR technology used to induce gene editing that could have significant clinical benefit,” said IGI Executive Director Jennifer Doudna, who was part of the team that invented CRISPR-Cas9, in an email. “The lasting positive impact on the edited cells shows incredible promise not only as a cure for sickle cell diseases but potentially other blood diseases.”

Sickle cell disease affects the blood by shaping the normal, red discoid shaped cells into inflexible and sharp sickle-shaped objects. The array of different sickle cell diseases have symptoms including sudden moments of pain, organ damage and anemia.

According to co-author and UC Berkeley researcher Mark Dewitt, mice were implanted with the CRISPR-edited human stem cells, which previously produced the mutated sickle cell gene. After four months, 2 percent of the implanted stem cells were retained in the mice. This percentage is significant because when the researchers previously ran the experiment, according to Dewitt, these cells would either be lost or only an insignificant amount would remain.“By doing our analysis at that time, we can see how effectively we corrected the stem cells. If these were put back into a human, they would go to the bone marrow and live there for the life of the person, producing corrected red blood cells continuously,” said co-author and University of Utah professor Dana Carroll in an email.

Because of the success in mice, this finding could eventually inform the treatment of sickle cell disease and other blood diseases.  This level of editing is sufficient to achieve a clinical benefit, Dewitt said.

Researchers hope to increase the rate of stem cell retention and eventually scale up to human subjects.

The current efficiency of the project is low, according to Dewitt.

“If everything goes according to plan, it could go great,” Dewitt said. “There’s certain places in the genome that you really don’t want to cut. We have to make sure that none of the cells die or worse, turn into cancer.”

Contact Edward Booth at [email protected] and follow him on Twitter at @Edward_E_Booth.