Base editing of haematopoietic stem cells rescues sickle cell disease in mice.

ABSTRACT: Sickle cell disease (SCD) is caused by a mutation in the β-globin gene HBB¹. We used a custom adenine base editor (ABE8e-NRCH)^2,3 to convert the SCD allele (HBB^S) into Makassar β-globin (HBB^G), a non-pathogenic variant^4,5. Ex vivo delivery of mRNA encoding the base editor with a targeting guide RNA into haematopoietic stem and progenitor cells (HSPCs) from patients with SCD resulted in 80% conversion of HBB^S to HBB^G. Sixteen weeks after transplantation of edited human HSPCs into immunodeficient mice, the frequency of HBB^G was 68% and hypoxia-induced sickling of bone marrow reticulocytes had decreased fivefold, indicating durable gene editing. To assess the physiological effects of HBB^S base e

SUBMITTER: Newby GA 

PROVIDER: S-EPMC8266759 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature