美国斯坦福大学Matthew H. Porteus、Daniel P. Dever等研究人员合作发现，用β-球蛋白替代α-球蛋白可治疗地中海贫血 。相关论文于2021年3月18日在线发表于国际学术期刊《自然—医学》。

据研究人员介绍，β-地中海贫血的病理发生不仅是由于β-球蛋白（HBB）的丧失，而且还由于β-球蛋白结合伴侣α-球蛋白（HBA1/2）的红细胞毒性积累和聚集。

Title: Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells

Author: M. Kyle Cromer, Joab Camarena, Renata M. Martin, Benjamin J. Lesch, Christopher A. Vakulskas, Nicole M. Bode, Gavin Kurgan, Michael A. Collingwood, Garrett R. Rettig, Mark A. Behlke, Viktor T. Lemgart, Yankai Zhang, Ankush Goyal, Feifei Zhao, Ezequiel Ponce, Waracharee Srifa, Rasmus O. Bak, Naoya Uchida, Ravindra Majeti, Vivien A. Sheehan, John F. Tisdale, Daniel P. Dever, Matthew H. Porteus

Issue&Volume: 2021-03-18

Abstract: β-Thalassemia pathology is due not only to loss of β-globin (HBB), but also to erythrotoxic accumulation and aggregation of the β-globin-binding partner, α-globin (HBA1/2). Here we describe a Cas9/AAV6-mediated genome editing strategy that can replace the entire HBA1 gene with a full-length HBB transgene in β-thalassemia-derived hematopoietic stem and progenitor cells (HSPCs), which is sufficient to normalize β-globin:α-globin messenger RNA and protein ratios and restore functional adult hemoglobin tetramers in patient-derived red blood cells. Edited HSPCs were capable of long-term and bilineage hematopoietic reconstitution in mice, establishing proof of concept for replacement of HBA1 with HBB as a novel therapeutic strategy for curing β-thalassemia.

DOI: 10.1038/s41591-021-01284-y

Source: https://www.nature.com/articles/s41591-021-01284-y