The researchers used a modified version of the technique to correct the mutation in human bone-marrow stem cells. They were able to show that these edited healthy cells could survive long term in mice at a level that may be high enough to benefit human patients.
'We're very excited about the promise of this technology,' said Jacob Corn, a senior author on the study and scientific director of the Innovative Genomics Initiative, which conducted the joint study between University of California, Berkeley, and the University of California San Francisco (UCSF). '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.'
Sickle-cell anaemia is caused by a single mutation in the gene that codes for haemoglobin protein. This mutation causes the characteristic 'sickle-shaped' blood cells which cause blockages in blood vessels, pain, and organ failure.
There have been previous attempts to use CRISPR/Cas9 to remove the mutated sickle-cell gene and insert a correct version of the gene into the bone-marrow stem cells. However, gene insertion is often unsuccessful in these slow-dividing stem cells.
They then infused mice with one million edited cells to test if the healthy gene would be maintained long term. Although cells with mutated DNA were more successful at proliferating, after 16 weeks an average of 2.3 percent of the edited cells remained in five mice.
Although this is a low percentage, evidence suggests that even this small change can have a positive effect on a person with the disease.
'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,' said co-author Dr Mark Walters, a paediatric haematologist and oncologist and director of UCSF Benioff Oakland’s Blood and Marrow Transplantation Program.
Other scientists caution that this level may not be sufficient. 'This is an important incremental step in bringing this sort of gene therapy to the clinic, but you need a little higher rate of correction to make it a therapy that is likely to be successful,’ Dr John Strouse, a haematologist at Duke University who was not involved in the study, told the Los Angeles Times.
The researchers say that years of study will be needed before the genome-editing could be safely introduced in humans.
The study was published in the current issue of Science Translational Medicine.