Adenine base editing efficiently restores the function of Fanconi anemia hematopoietic stem and progenitor cells.

ABSTRACT: Fanconi Anemia (FA) is a debilitating genetic disorder with a wide range of severe symptoms including bone marrow failure and predisposition to cancer. CRISPR-Cas genome editing manipulates genotypes by harnessing DNA repair and has been proposed as a potential cure for FA. But FA is caused by deficiencies in DNA repair itself, preventing the use of editing strategies such as homology directed repair. Recently developed base editing (BE) systems do not rely on double stranded DNA breaks and might be used to target mutations in FA genes, but this remains to be tested. Here we develop a proof of concept therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells. We find that optimizing adenine base editor construc

SUBMITTER: Siegner SM 

PROVIDER: S-EPMC9653444 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature