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WASHINGTON, Jan. 11 (Xinhua) -- U.S. researchers have taken an important step toward using the powerful gene editing tool CRISPR-Cas9 to cure a rare genetic immunodeficiency disorder called chronic granulomatous disease (CGD) and perhaps other blood disorders.
Researchers from the U.S National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, said Thursday they have successfully harnessed the CRISPR-Cas9 technology to repair the disease-causing mutation in blood-forming stem cells taken from CGD patients.
After transplant into mice, the repaired stem cells developed into normally functioning white blood cells for up to five months, with no signs of side effects, according to their study published in the U.S. journal Science Translational Medicine.
"The most exciting finding in the study was that the gene-repaired stem cells that functioned as normal cells continued to do so after transplant into mice, indicating gene correction of long-term engrafting primitive stem cells," the researchers said in a statement.
"This is one finding that provides hope that this can be further developed into a clinical treatment in the future."
CGD is caused by mutations in the gene CYBB, which provides instructions for production of a protein called NOX2.
Defects in NOX2 impair the infection-fighting ability of white blood cells, leaving people with CGD highly susceptible to life-threatening infections.
While stem cell transplantation offers a potential therapy for CGD, the procedure carries a risk of toxicity and potentially lethal complications.
In the new study, NIAID researchers focused on a CYBB mutation in which a single change in the genetic code leads to production of inactive NOX2.
The investigators used CRISPR-Cas9 to specifically target and repair this mutation in blood-forming stem cells isolated from two CGD patients, restoring the defective CYBB sequence to the one that would appear in a healthy person.
The repaired stem cells from CGD patients continued to behave normally after transplant into immunodeficient mice, developing into white blood cells that produced functional NOX2 for up to five months.
The researchers said they did not detect any unintended effects resulting from the CRISPR-Cas9 gene editing.
"Although more work is needed, this study provides a proof-of-principle that this gene-editing strategy can repair small disease-causing mutations in blood-forming stem cells," they said.
The scientists planned to perform additional studies with the ultimate goal of developing this approach into a clinical treatment for people with CGD.
They suggested that this approach to gene correction also may be applicable to other blood diseases caused by mutations in a single gene, such as sickle-cell anemia.
