Therapeutic gene editing in CD34⁺ hematopoietic progenitors from Fanconi anemia patients.

ABSTRACT: Gene targeting constitutes a new step in the development of gene therapy for inherited diseases. Although previous studies have shown the feasibility of editing fibroblasts from Fanconi anemia (FA) patients, here we aimed at conducting therapeutic gene editing in clinically relevant cells, such as hematopoietic stem cells (HSCs). In our first experiments, we showed that zinc finger nuclease (ZFN)-mediated insertion of a non-therapeutic EGFP-reporter donor in the AAVS1 "safe harbor" locus of FA-A lymphoblastic cell lines (LCLs), indicating that FANCA is not essential for the editing of human cells. When the same approach was conducted with therapeutic FANCA donors, an efficient phenotypic correction of FA-A LCLs was obtained. Using primary cord blood CD34⁺ cells fro

SUBMITTER: Diez B 

PROVIDER: S-EPMC5666315 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature