Enhanced fetal hemoglobin production via dual-beneficial mutation editing of the HBG promoter in hematopoietic stem and progenitor cells for β-hemoglobinopathies.

ABSTRACT:

Background

Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased. However, achieving this goal requires precise nucleotide conversions in hematopoietic stem and progenitor cells (HSPCs) at therapeutic efficiency, which remains a challenge.

Methods

We employed Cas9 RNP-ssODN-mediated homology-directed repair (HDR) gene editing to mimic two naturally occurring HBG promoter point mutations; -175T > C, associated with high HbF l

SUBMITTER: Chandraprabha PB 

PROVIDER: S-EPMC11687217 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature