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

作者：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 · 发表于：Science Translational Medicine · 年份：2021 · DOI：10.1126/scitranslmed.abf2444 · 被引用次数：166 · 研究领域：Hemoglobinopathies and Related Disorders、CRISPR and Genetic Engineering、Virus-based gene therapy research

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.