Using CRISPR/Cas9 to edit long-lived blood stem cells can reverse symptoms and potentially provide long-term treatment in certain blood diseases.
CRISPR/Cas9 gene-editing technology has attracted significant attention for its potential to provide treatments and even cures for many different types of genetic disorders. The technology is quite new, however, and the long-term impacts and consequences of manipulating the genetic code using gene-editing tools is not yet known, making use of the technology in humans quite risky.
Scientists at the Fred Hutchinson Cancer Research Center may have found a way to reduce that risk when treating certain blood disorders. The researchers elected to edit only a specialized subset of adult stem cells, which are long-lived blood stem cells. CD90 cells are the source of all cells in the blood and immune system. By only targeting these cells for gene editing, they reduced the risk of unwanted effects associated with more general gene editing treatments, while also potentially reducing the cost of these types of therapies.
In a preclinical study, the scientists edited adult blood stem cells to correct for a genetic defect that influences how hemoglobin is produced. The editing involved the removal of a small section of DNA that prevents the production of fetal hemoglobin production. Over three-quarters of the targeted cells took up the edits and, when infused, the edited cells engrafted multiplied and produced blood cells, 30% of which also contained the edits. As a result, up to 20% of the red blood cells contained fetal hemoglobin, which is known to reverse disease symptoms in sickle cell disease and thalassemia. A phase I study in humans is in the planning stages.
The researchers also believe that the approach could be used to develop treatments for HIV and some cancers.