New Sickle Cell Gene-Editing Research Published in The New England Journal of Medicine

Sickle cell disease is an inherited blood disorder that has long been associated with severe pain, frequent hospitalizations and few curative options for pediatric patients. New research published in The New England Journal of Medicine offers encouraging evidence for further advances in sickle cell therapies.

Christopher McKinney, MD, a pediatric hematologist and co-author of the study, specializes in caring for both children and adults with sickle cell disease. Dr. McKinney is a part of a collaborative group of physicians and scientists examining innovative gene therapies for sickle cell disease. This approach is designed to prevent sickle cell complications at their source.

CRISPR gene editing for sickle cell disease

Researchers at sites across the country evaluated renizgamglogene autogedtemcel (reni-cel), an investigational CRISPR-based gene-editing therapy, in adolescents and adults with severe sickle cell disease. The treatment involves using the patient’s own blood-forming stem cells and modifying them to increase production of fetal hemoglobin and prevent red blood cells from becoming sickle-shaped. Reni-cel requires just one infusion to work, and uses a first-in-human next generation CRISPR technology that targets different parts of the genome with high specificity and few off-target cuts. A total of 28 patients with the condition received this therapy after undergoing standard chemotherapy conditioning.

Six months post-treatment, patients experienced near-normal total hemoglobin levels and a large, sustained increase in fetal hemoglobin. While adverse effects remained consistent after chemotherapy and stem-cell transplantation, 27 out of 28 patients reported no severe pain crises or pain episodes during the follow-up period. Results highlight the utility of alternative strategies to increase fetal hemoglobin production and the need for more approaches that optimize safety and on-target editing in these evolving therapies.

“The reni-cel results reflect the rapid evolution and broadening landscape of treatment strategies for patients with sickle cell disease,” Dr. McKinney says. “As gene-editing approaches continue to advance, we look forward to the next major advances, including the potential for in vivo therapies.”