Scientists, using the CRISPR-Cas9 gene editing tool, have found a way to fix the mutated gene responsible for sickle cell disease, which leads to anemia, painful blood blockages and early death.
For the first time, researchers have corrected the mutation in a proportion of stem cells that is high enough to produce a substantial benefit in sickle cell patients.
They hope to re-infuse patients with the edited stem cells and alleviate symptoms of the disease, which primarily afflicts those of African descent.
“There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease,” said Jacob Corn, from University of California, Berkeley.
In tests in mice, the genetically engineered stem cells stuck around for at least four months after transplantation, an important benchmark to ensure that any potential therapy would be lasting.
“This is an important advance because for the first time we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said Mark Walters, from University of California, San Francisco.
Sickle cell disease is a recessive genetic disorder caused by a single mutation in both copies of a gene coding for beta-globin, a protein that forms part of the oxygen-carrying molecule hemoglobin.
This homozygous defect causes hemoglobin molecules to stick together, deforming red blood cells into a characteristic “sickle” shape.
These misshapen cells get stuck in blood vessels, causing blockages, anemia, pain, organ failure and significantly shortened lifespan.
Sickle cell disease is particularly prevalent in African-Americans and the sub-Saharan African population, affecting hundreds of thousands of people worldwide.
Researchers aimed to develop genome engineering-based methods for correcting the disease-causing mutation in each patient’s own stem cells to ensure that new red blood cells are healthy.
The team used CRISPR-Cas9 to correct the disease-causing mutation in hematopoietic stem cells – precursor cells that mature into red blood cells – isolated from whole blood of sickle cell patients. The corrected cells produced healthy hemoglobin, which mutated cells do not make at all.
“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Corn said.
“It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases,” he said.
The findings were published in the journal Science Translational Medicine.