Sickle Cell Disease Mutation Repaired in Patient Cells With Prime Editing

In Nature Biomedical Engineering, investigators with the Broad Institute's Merkin Institute of Transformative Technologies in Healthcare, Harvard University, and other centers present findings from an ex vivo prime editing study focused on repairing a sickle cell disease (SCD)-related mutation in the beta-globulin-coding gene HBB. After achieving prime editing frequencies of between 15 percent and 41 percent in hematopoietic stem cells or progenitor cells from four SCD-affected individuals, the researchers transplanted cells into immunodeficient mice, tracking edited cell engraftment, wild-type HBB levels, potential off-target edits, and response to low oxygen conditions after 17 weeks. "Taken together, our results establish an early example of therapeutic prime editing in human HSCs and demonstrate a potential strategy for a one-time autologous SCD treatment that directly corrects the sickle globin allele back to wild-type HBB without requiring [double-strand breaks] or donor DNA templates," the authors suggest.