Scientists repair gene defect in stem cells from patients with rare immunodeficiency

January 11, 2017, NIH/National Institute of Allergy and Infectious Diseases
Researchers have harnessed the CRISPR-Cas9 technology to correct mutations in the blood stem cells of patients with a rare immunodeficiency disorder; the engineered cells successfully engrafted in mice for up to five months. Credit: Chris Bickel / Science Translational Medicine (2017)

Scientists have developed a new approach to repair a defective gene in blood-forming stem cells from patients with a rare genetic immunodeficiency disorder called X-linked chronic granulomatous disease (X-CGD). After transplant into mice, the repaired stem cells developed into normally functioning white blood cells, suggesting the strategy could potentially be used to treat people with this disease.

X-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 , leaving people with X-CGD highly susceptible to life-threatening infections. In the study, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, focused on a CYBB mutation in which a single change in the genetic code leads to production of inactive NOX2.

The investigators used the gene editing tool CRISPR-Cas9 to specifically target and repair this mutation in blood-forming stem cells isolated from two X-CGD patients. Their targeted gene-repair method restored the defective CYBB sequence to the sequence that would appear in a healthy person, rendering the corrected gene indistinguishable from the normal gene. The researchers did not detect any unintended effects resulting from the CRISPR-Cas9 gene editing. Other gene therapy approaches that seek to restore the function of a mutated gene often introduce additional changes, including addition or loss of genetic material.

The repaired stem cells from X-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 authors note that although more work is needed, this study provides a proof-of-principle that this gene-editing strategy can repair small disease-causing mutations in .

The scientists plan to perform additional studies with the ultimate goal of developing this approach into a clinical treatment for people with X-CGD. They suggest 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.

The study is published in Science Translational Medicine.

Explore further: Scientists edit gene mutations in inherited form of anemia

More information: "CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease," stm.sciencemag.org/lookup/doi/ … scitranslmed.aah3480

Related Stories

Scientists edit gene mutations in inherited form of anemia

October 26, 2016
A Yale-led research team used a new gene editing strategy to correct mutations that cause thalassemia, a form of anemia. Their gene editing technique provided corrections to the mutations and alleviated the disease in mice, ...

Gene editing of blood stem cells can correct disease-causing mutations

September 23, 2016
Recent advances in gene editing technology, which allows for targeted repair of disease-causing mutations, can be applied to hematopoietic stem cells with the potential to cure a variety of hereditary and congenital diseases. ...

Scientists show how mutation causes incurable premature aging disease

October 31, 2016
Scientists have demonstrated how a mutation in a specific protein in stem cells causes an incurable premature aging disease called dyskeratosis congenita, and were able to introduce the mutation into cultured human cells ...

Genome engineering paves the way for sickle cell cure

October 12, 2016
A team of physicians and laboratory scientists has taken a key step toward a cure for sickle cell disease, using CRISPR-Cas9 gene editing to fix the mutated gene responsible for the disease in stem cells from the blood of ...

Researchers take step toward gene therapy for sickle cell disease

November 7, 2016
A team of researchers at the Stanford University School of Medicine has used a gene-editing tool known as CRISPR to repair the gene that causes sickle cell disease in human stem cells, which they say is a key step toward ...

CRISPR gene editing reveals new therapeutic approach for blood disorders

August 15, 2016
An international team of scientists led by researchers at St. Jude Children's Research Hospital has found a way to use CRISPR gene editing to help fix sickle cell disease and beta-thalassemia in blood cells isolated from ...

Recommended for you

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.