Efficient and <i>in situ</i> correction of hemoglobin Constant Spring mutation by prime editing in human hematopoietic cells.

ABSTRACT: Hemoglobin Constant Spring (Hb CS) is the most common non-deletional and clinically significant α-thalassemic mutation, and it is caused by an anti-termination mutation at the α2-globin gene stop codon. We developed a prime editing strategy for the creation and correction of Hb CS. We showed that prime editing could efficiently introduce Hb CS mutations in both human erythroblast cell lines (an average frequency of 32%) and primary hematopoietic stem and progenitor cells (HSPCs) from healthy donors (an average frequency of 27%). By targeting the established Hb CS homozygous erythroblasts, we achieved an average frequency of 32% in situ correction without selection. Notably, prime editing corrected the Hb CS mutation to wild type at an average frequency of 21% in HSPCs from three pat

SUBMITTER: Shao C 

PROVIDER: S-EPMC11617223 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature