Gene editing technology and clinical expertise enabled researchers to correct the genetic mutation that causes sickle cell disease in stem cells. Clinical trials will likely follow soon.

A team of physicians and laboratory scientists has taken a significant step toward a cure for sickle cell disease, the deadly and painful genetic disorder that affects millions of people worldwide, primarily those of African descent. The disease leads to anemia, painful blood blockages and early death.

“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 anemia,” says Mark Walters, MD, a pediatric hematologist and oncologist and director of UCSF Benioff Children’s Hospital Oakland’s Blood and Marrow Transplantation Program.

Dr. Walters joined with researchers from the University of California, Berkeley, and the University of Utah School of Medicine to co–author an article on the results of their work. The study, "Selection–free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells,” was published in the Oct. 12 issue of the journal Science Translational Medicine.

To correct the mutation, the researchers modified hematopoietic stem cells from patients with sickle cell disease using the CRISPR/Cas9 gene editing technology, which enables geneticists and medical researchers to target and mutate one or more genes in the genome of a cell. The research team showed that the corrected stem cells successfully engrafted in a mouse model and produced enough normal hemoglobin to have a potential clinical benefit. Moreover, the genetically engineered stem cells stuck around for at least four months after transplantation, an important benchmark to ensure that any potential therapy would be lasting. The goal is to further develop these genome engineering–based methods for correcting the disease–causing mutation in each patient’s own stem cells.

“We’re very excited about the promise of this technology,” says Jacob Corn, PhD, the study’s senior author and scientific director of the Innovative Genomics Initiative at UC Berkeley. “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.”

The researchers emphasize that future preclinical work will require additional optimization, large–scale mouse studies and rigorous safety analysis. Corn and his lab have joined with Walters, an expert in developing curative treatments such as bone marrow transplant and gene therapy for sickle cell disease, to initiate an early–phase clinical trial to test this new treatment within the next five years. To that end, the team – which also includes researchers from UCLA – recently received a grant of more than $4 million from the California Institute for Regenerative Medicine to support preclinical development of the therapy over 30 months, beginning in February 2017.

Research groups might be able to apply the approach described in this study to develop treatments for other blood diseases, such as beta–thalassemia, severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), rare disorders like Wiskott–Aldrich syndrome (WAS) and Fanconi anemia, and even HIV infection.

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” Corn says. “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.”