Gene editing of human blood-forming stem cells mimics a benign genetic condition that helps to overcome sickle cell disease and other blood disorders

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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 patients. The study, which appears online today in Nature Medicine, provides proof-of-principle for a new approach to treat common blood disorders by genome editing.

“Our approach to gene editing is informed by the known benefits of hereditary persistence of foetal haemoglobin,” said Mitchell J. Weiss, M.D., Ph.D., chair of the St. Jude Department of Haematology and one of the study’s lead authors. “It has been known for some time that individuals with genetic mutations that persistently elevate foetal haemoglobin are resistant to the symptoms of sickle cell disease and beta-thalassaemia, genetic forms of severe anaemia that are common in many regions of the world. We have found a way to use CRISPR gene editing to produce similar benefits.”

Foetal and adult haemoglobin are two different versions of our favourite oxygen transport molecule. After birth, as adult haemoglobin levels rise, diseases that affect the adult molecule like sickle cell or beta-thalassaemia can become apparent. Both conditions affect the survival of red blood cells and inhibit oxygen delivery to tissues, which can lead to impaired function of different organs with devastating consequences for patients.

This new study has identified a potential DNA target for gene editing that raises the levels of foetal haemoglobin in adults. “We have been able to snip that DNA target using CRISPR, remove a short segment in a “control section” of DNA that stimulates gamma-to-beta switching, and join the ends back up to produce sustained elevation of fetal hemoglobin levels in adult red blood cells”, explained Weiss. 

When the scientists edited the DNA of blood-forming stem cells derived from patients with sickle cell disease, they were able to activate those genes and produce red blood cells that had enough fetal hemoglobin to be healthy.