Targeted knock-in of NCF1 cDNA into the NCF2 locus leads to myeloid phenotypic correction of p47 ^phox -deficient chronic granulomatous disease.

ABSTRACT: p47 ^phox -deficient chronic granulomatous disease (p47-CGD) is a primary immunodeficiency caused by mutations in the neutrophil cytosolic factor 1 (NCF1) gene, resulting in defective NADPH oxidase function in phagocytes. Due to its complex genomic context, the NCF1 locus is not suited for safe gene editing with current genome editing technologies. Therefore, we developed a targeted NCF1 coding sequence knock-in by CRISPR-Cas9 ribonucleoprotein and viral vector template delivery, to restore p47 ^phox expression under the control of the endogenous NCF2 locus. NCF2 encodes for p67 ^phox , an NADPH oxidase subunit that closely interacts with p47 ^phox and is predominantly expressed in myeloi

SUBMITTER: Siow KM 

PROVIDER: S-EPMC11215332 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature