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Discontinued CRISPR gene therapy for sickle-cell disease improves symptoms
Nature Medicine explores the latest translation and clinical research news, with results from a clinical trial of Novartis' discontinued gene therapy to restore fetal hemoglobin.
Three adult patients with severe sickle-cell disease have been treated with a CRISPR–Cas9-based gene therapy that genetically modifies autologous blood stem cells to induce fetal hemoglobin expression. The phase 1/2 clinical trial of Novartis' OTQ923 showed successful engraftment of the genetically modified cells in all three patients. Between 19% and 27% of the patients’ hemoglobin was of the fetal γ-globin type after treatment — a significant increase from pretreatment levels of 0.4% to 1.4%. Up to 88% of red blood cells were positive for fetal hemoglobin after treatment. Although the patients showed clinical improvement, all three continued to have mild hemolysis and some symptoms of sickle-cell disease. The study did not find substantial off-target genetic effects of CRISPR–Cas9.