Researchers have had further success using the CRISPR/Cas9 genome-editing technique to repair the mutation that causes sickle-cell anaemia.
The team used CRISPR/Cas9 to replace the faulty gene in stem cells from patients with the disease. The healthy cells were injected into mice and were still working efficiently 16 weeks later.
‘What we’ve finally shown is that we can do it,’ said Dr Matthew Porteus of Stanford University, who led the study. ‘It’s not just on the chalkboard. We can take stem cells from a patient and correct the mutation and show that those stem cells turn into red blood cells that no longer make sickle haemoglobin.’
Sickle-cell anaemia is an inherited disease in which a mutation in the haemoglobin gene causes red blood cells to become sickle-shaped, rigid and sticky. This causes blockages, reducing blood flow and depriving that part of the body of oxygen, which in turn leads to pain, anaemia and ultimately organ damage.
The research, which was published in Nature, used CRISPR to correct the mutation in haematopoietic stem cells (used to make blood cells) of patients with the disease. The faulty DNA was removed and a correct version of the gene inserted using a virus.
Last month, researchers at the University of California, Berkeley, also used CRISPR to correct the sickle-cell mutation in human stem cells. They used the genome-editing technique to both delete the faulty gene and insert the healthy gene, achieving a 25 percent success rate.
In the latest study, the Stanford team created a concentrated pool of stem cells in which 90 percent had the corrected gene. These were injected into mice, and 16 weeks later the healthy stem cells were still thriving.
‘These stem cells have a property to be able to get from the blood system into the bone marrow where they then set up shop and start making other blood cells,’ said Dr Porteus.
It is not necessary to replace all the diseased blood cells for this procedure to be successful. Dr Porteus says that patients with a proportion of sickle cells below 30 percent will show no symptoms of the disease. Sickle cells have an average life of just ten days compared with 120 days for healthy cells, so the number of corrected red blood cells being produced by the bone marrow soon overtakes the number of sickle cells.
‘We think we have a complete data set to present to the FDA (Food and Drug Administration) to say we’ve done all pre-clinical experiments to show this is ready for a clinical trial,’ Dr Porteus told Reuters. The Stanford team hopes to test the technique on the first set of patients in 2018.