CRISPR-Cas9 Making Moves in Sickle Cell Disease

Researchers have reported that, using CRISPR-Cas9 technology, they were able to correct the sickle cell mutation in mice infected with sickle cell disease (SCD), suggesting that gene editing could be an option for treating the cause of the disease, rather than the symptoms.

The edited genes were still detectable 16 weeks later, according to the study results, which were published in Science Translational Medicine.

“What we have right now, if we can scale it up and make sure it works well, is already enough to form the basis of a clinical trial to cure SCD with gene editing,” the study’s lead author Mark DeWitt, PhD, of the Innovative Genomics Initiative at University of California, Berkeley, said in a press release. Dr. DeWitt added that SCD is an ideal target to test this technology because it occurs when a single letter in the HBB gene is a T instead of an A.

Researchers used CRISPR-Cas9 technology to revert a portion of mutant sickle cell genes in the hematopoietic/progenitor cells obtained from the blood of SCD patients, then assessed how these altered human cells would survive in mice by transplanting approximately 1 million of the cells into each mouse in the study. Approximately 12 percent of the stem cells were fully altered by CRISPR.

After 16 weeks, the researchers tested human blood cells in the bone marrow of five mice and found that, on average, 2.3 percent of these cells had the edited DNA with the SCD trait.

“It will take years of very careful and rigorous study to ensure that it’s totally and completely safe before we even contemplate an actual clinical trial,” said Dr. DeWitt. The authors noted that they will need to scale up the gene-editing abilities for this approach to be feasible, since a human would need hundreds of millions of cells. In addition, they need to be sure that CRISPR does not unexpectedly affect other parts of the human genome.

Sources: DeWitt MA, Magis W, Bray NL, et al. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. Sci Transl Med. 2016;8 :360ra134; The Los Angeles Times, October 12, 2016.