Sickle cell disease (SCD) is a group of blood disorders, including sickle cell anaemia, that is caused by stem blood cells producing mutated red blood cells. This leads to health complications, as the odd shaped blood cells get trapped in small blood vessels, and can be fatal.
Now a team of researchers from several institutions have used the gene editing technique CRISPR to edit out the mutation that leads to SCD, raising hope that the method could be used to treat other major blood diseases.
Researchers have focused on SCD not only because it is thought to affect around 3.2 million people globally, with an additional 43 million carrying the trait, but also because it is all caused by a single gene mutation. This means that, theoretically at least, it is much easier to treat than other genetic diseases, and should be an easy target for the precision gene editing tool CRISPR-Cas9.
By first priming the CRISPR modules to seek out the single gene mutation, they then took blood samples from mice afflicted with SCD and isolated from these the blood stem cells that will eventually give rise to the mutated red blood cells.
Using CRISPR on these precursor cells, the theory is that the modules will enter the cells (with a little help from the researchers), seek out the gene mutation, remove it, and then replace it with a healthy version so that when a stem cell comes to produce more red blood cells, they will no longer be the harmful sickle shape.
The scientists were able to get the CRISPR modules into around 25 percent of the stem cells. When these were then transplanted back into the mice, they found that around 6 percent of the stem cells retained the healthy gene inserted by CRISPR, and went on to produce normal shaped red blood cells.
This may not sound like it was particularly successful, but even a boost in red blood cells of just 5 percent is enough for patients to feel the benefit and dramatically improve their health.
The stem cells survived in the body for around four weeks, at which point they were replaced by newer stem cells, which revert to the sickle cell mutation, meaning patients would need to be treated again.
“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 anaemia,” explained Mark Walters, who co-authored the paper published in Science Translational Medicine.
The hope is to move towards a clinical trial in humans and develop a new therapy, but it could also lead to developments in treating other diseases.
“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” said senior author Jacob Corn. “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.”