Researchers led by Rice University used CRISPR to correct the sickle cell mutation in up to 40% of stem cells taken from affected patients. While promising, the work also highlights the hurdles that must be cleared before gene editing can become a reality for patients with blood disorders.
CRISPR is an appealing approach for sickle cell disease, which is caused by a single mutation in the gene that codes for beta-globin, a component of red blood cells. Gang Bao, a bioengineering professor at Rice University, detailed a series of tests exploring the use of CRISPR to fix this mutation at the American Association for the Advancement of Science’s annual meeting.
The researchers zeroed in on stem cells and progenitor cells, which can differentiate into a more limited range of cell types than stem cells: "The idea is to correct that particular mutation, and then stem cells that have the correction would differentiate into normal blood cells, including red blood cells. Those will then be healthy blood cells,” Bao said.
Alongside colleagues from Baylor College of Medicine and Texas Children’s Hospital, Bao’s team gathered stem and progenitor cells from patients with sickle cell disease and used CRISPR to correct the mutation. They were able to repair between 20% and 40% of the cells.
A team at Matt Porteus’s lab at Stanford then injected the edited cells into the bone marrow of mice, where they persisted after 19 weeks.
"The rate of repair remained stable, which is great," Bao said.
While a step in the right direction, the research highlights some obstacles. These include tweaking the method to prevent unintended off-target effects and trying to repair a higher proportion of stem cells, as the team is unsure if correcting 40% is enough to cure a patient.
Gene therapy for sickle cell and other blood disorders has been ramping up. Vertex Pharmaceuticals teamed up with CRISPR Therapeutics in 2015, and recently licensed the first CRISPR-based treatment to come out of the partnership: a therapy for beta thalassemia and sickle cell.