Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells.

ABSTRACT: Sickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible TALEN-mediated gene editing process enabling efficient HBB correction via a DNA repair template while minimizing risks associated with HBB inactivation. Comparing viral versus non-viral DNA repair template delivery in hematopoietic stem and progenitor cells in vitro, both strategies achieve comparable HBB correction and result in over 50% expression of normal adult hemoglobin in red blood cells without inducing β-thalassemic phenotype. In an immunodeficient female mouse model, transplanted cells edited with the non-viral strategy exhibit higher engraftment and gene correction levels compared to those edited with the viral

SUBMITTER: Moiani A 

PROVIDER: S-EPMC11166989 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature