CRISPR technology to cure sickle cell disease

CRISPR technology to cure sickle cell disease

Credit: University of Illinois at Chicago

University of Illinois Chicago is one of the U.S. sites participating in clinical trials to cure serious red blood congenital diseases, such as sickle cell anemia or thalassemia, by safely modifying the DNA of patients’ blood cells.

The first cases treated with this approach were recently published in an article co-authored by Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the UIC College of Medicine. The article reports that two patients have been cured beta thalassemia and sickle cell disease after their own genes were processed with CRISPR-Cas9 technology. The two researchers who invented this technology were awarded the Nobel Prize in Chemistry in 2020.

In the paper published in the New England Journal of Medicine, CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia, researchers reported that gene editing stem cells by deleting the gene BCL11A, the gene responsible for suppressing fetal hemoglobin production. By doing this, stem cells begin to produce fetal hemoglobin so that patients with congenital hemoglobin defects (beta thalassemia or sickle cell disease) make enough fetal hemoglobin to overcome the effect of the defective hemoglobin causing their disease.

The advantage of this approach is that it uses the patient’s cells without the need for a donor. Also, the gene engineering does not use a viral vector as in other gene therapy studies, but is done with electroporation (rapid production of pores in the cells at high voltage) which is known to have a low risk of activating genes outside of the target, according to Rondelli.

Sickle cell disease is an inherited abnormality of the hemoglobin that causes the red blood cells become crescent-shaped. These cells can lyse and clog small blood vessels, depriving body tissues of oxygen. The disease can cause extreme pain and damage the lungs, heart, kidneys and liver. Beta thalassemia is a blood disease that decreases the production of hemoglobin – the iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low hemoglobin levels lead to a lack of oxygen in many parts of the body.

The first two patients to receive the treatment had successful results and are still being monitored. Rondelli is on the steering committee of an international clinical trial, with UIC being the only site in Chicago. Although the study is still in its early stages and the first patients will be followed for some time before the number expands worldwide, UIC will be one of the few sites ready for this treatment.

“It is a great privilege for UIC to be part of this international study and I hope that in the future we will have our own patients undergo this procedure,” said Rondelli.

“UIC and UI Health are an ideal place for any cell therapy for sickle cell disease because of our experience and success in stem cell transplantation in these patients. In fact, more than 75% of sickle cell patients can be cured with a transplant, and we have already done more than 50 cases,” “he said.

While a full match donor is still the first line of treatment, finding a compatible stem cell donor is challenging. For this reason, many centers, including UI health, have developed strategies to successfully use donors that are only 50% compatible, the so-called haplo-identical donors. However, according to Rondelli, in about 30% to 50% of patients there are still multiple barriers that can limit the possibility of a donor-derived transplant, such as the availability of a family donor or the presence of antibodies in the patient caused by many previous transfusions of red blood cells, which are said to reject donor stem cells.

“This gene editing procedure has the potential to overcome all of these factors. Cells from the same patient can be manipulated and transplanted without the risk of rejection or causing immune responses from the donor (graft versus host disease),” said Rondelli. “For the nearly 900 patients with SC coming to our hospital, this should be great news.”

Patients who will participate in the trial in the future will have cells sent to the CRISPR manufacturing site where the cells undergo genetic engineering. Patients then receive chemotherapy prior to the edited strain cells reintroduced into their bloodstream.

Researchers hope this treatment can be a game changer for world health. Sickle cell disease and beta thalassemia and other congenital blood disorders are major diseases in the world. Rondelli said 5 million people in Nigeria alone are affected sickle cell disease, and many others in Africa. Also, currently 30% of transplants performed in India, which numbers 1.3 billion people, are for the treatment of severe beta thalassemia, he added.

“The hope is that this treatment will be accessible and affordable in many low-middle-income countries, the Middle East, Africa and India, and will have a significant impact on the lives of many people in these areas,” said Rondelli.

Two studies show promising results with gene therapies targeting sickle cell anemia

More information:
Haydar Frangoul et al, CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia, New England Journal of Medicine (2020). DOI: 10.1056 / NEJMoa2031054

Quote: CRISPR Technology to Cure Sickle Cell Disease (2021, January 21) Retrieved April 30, 2021 from

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