Editing the DNA of human blood cells has the potential to significantly reduce the impact of hereditary blood diseases such as sickle cell anaemia and thalassaemia, according to researchers from Australia and the United States. In their study, published this month (14 May) in Nature Communications, the researchers demonstrate that a benign mutation can be artificially introduced into red blood cells. The result could be a reduction in the symptoms of blood diseases, they say.
Hereditary blood diseases like sickle cell are caused by mutations in the genes that produce haemoglobin. In the case of sickle cell, the inheritance of two mutant genes – one from each parent – causes haemoglobin to form long strands. These twist blood cells into rigid crescent shapes, which can restrict blood flow, leading to pain and organ damage.
Similarly, thalassaemia causes abnormal haemoglobin production that leads to the destruction of red blood cells. Both diseases are common in Africa and the Middle East, and sickle cell alone kills nearly 200,000 people a year. In the womb, babies create a form of haemoglobin that is different from the one in adults, which allows a foetus to take on oxygen from the mother’s blood. If produced in patients with genetic blood disorders, this foetal haemoglobin has the potential to compensate for their faulty adult version, reducing symptoms.
The DNA mutation that produces the helpful haemoglobin can be introduced into cells by using particular proteins that cut into the target cell’s DNA. “Breaks in DNA can be lethal to cells, so they have in-built machinery to repair any nicks as soon as possible by grabbing any spare DNA that seems to match – much like you might darn a red sock with any spare red wool lying around,” explains Merlin Crossley, a biochemist at the University of New South Wales in Australia and co-author of the paper.
The technique has been tested only on blood cells cultured in the laboratory. If future tests show that it can be used safely on extracted blood stem cells, the technique might be used as a treatment, the researchers say. The potential advantages of this treatment is that it has no side-effects, is less intrusive and could be cheaper than the regular medications and blood transfusions commonly used to treat blood disorders, according to the authors. Crossley notes, however, that editing DNA would be difficult in developing countries because it requires expensive medical technology.
As scientists develop a better understanding of how haemoglobin genes function, cheaper and more practical solutions could be developed, he says. Yuet Kan, a human geneticist at the University of California in the United States, says the study demonstrates the potential of genetic editing to treat some hereditary diseases. But he says that to become a therapeutic reality, more work must be done to better target the DNA editing, and improve science’s ability to modify enough cells to be transplanted back into the patient.