Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease

著者: Annalisa Lattanzi, Joab Camarena, Premanjali Lahiri, Helen Segal, Waracharee Srifa, Christopher A. Vakulskas, Richard L. Frock, Josefin Kenrick, Ciaran M. Lee, Narae Talbott, Jason Skowronski, M. Kyle Cromer, Carsten T. Charlesworth, Rasmus O. Bak, Sruthi Mantri, Gang Bao, David DiGiusto, John F. Tisdale, J. Fraser Wright, Neehar Bhatia, Maria Grazia Roncarolo, Daniel P. Dever, Matthew H. Porteus - Science Translational Medicine 2021 被引用: 160

allelic correction in clinical-scale gcHBB-SCD manufacturing. After transplant into immunodeficient NSG mice, 20% gene correction was achieved with multilineage engraftment. The long-term safety, tumorigenicity, and toxicology study demonstrated no evidence of abnormal hematopoiesis, genotoxicity, or tumorigenicity from the engrafted gcHBB-SCD drug product. Together, these preclinical data support the safety, efficacy, and reproducibility of this gene correction strategy for initiation of a phase 1/2 clinical trial in patients with SCD.