Hemoglobinopathies

In a multicenter gene editing study of sickle cell disease (SCD) published in July in Nature, a team led by researchers from St. Jude’s Children’s Hospital and the Broad Institute of Harvard and MIT reported promising results of research into a base editing technique that avoids certain risks encountered with other gene editing approaches. In SCD, thymine (T) replaces adenine (A) at a key location in the HBB gene. Base editing can convert T to cytosine (C), producing Hb-Makassar, a nonpathogenic variant. The investigators used an adenine base editor, a molecular tool that recognizes the mutated position on HBB and converts T to C. After this base editor was used on stem cells from patients with SCD, 80% of the patients had their HBB gene converted to the Makassar variant. At 16 weeks post transplantation, 68% of the donor-derived stem cells had HBBS genes edited to Hb-Makassar, and sickling was significantly reduced in red blood cells derived from these stem cells. A murine model of this technique showed greatly improved SCD symptoms in mice that received transplants of base-edited stem cells, with no side effects from the gene-editing process.