Neutrophil cytosolic factor 1 (NCF1) (NCF1)

Neutrophil cytosolic factor 1 (NCF1), also known as p47-phox, is a critical 47 kDa cytosolic subunit of the multi-protein nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex (UniProt: P14598). In professional phagocytes, NCF1 is essential for the respiratory burst, a process where the oxidase complex assembles at the membrane to produce superoxide and other reactive oxygen species (ROS) to destroy ingested pathogens (NCBI Gene: 653361). Mutations in the NCF1 gene are the primary cause of the autosomal recessive form of Chronic Granulomatous Disease (CGD), which accounts for approximately 25% of all CGD cases and leads to life-threatening bacterial and fungal infections (Roesler et al., 2000). The therapeutic strategy involving the NCF1 gene in autologous CD34+ hematopoietic stem cells (HSCs) focuses on ex vivo gene therapy to cure p47-phox-deficient CGD. This process involves harvesting a patient's own HSCs, using a lentiviral vector to insert a functional copy of the NCF1 gene, and re-infusing the modified cells into the patient (Santilli et al., 2011). Once engrafted, these stem cells differentiate into functional neutrophils and macrophages that express the p47-phox protein, thereby restoring the NADPH oxidase activity and the host's ability to combat infections (Kohn et al., 2023). This approach aims to provide a long-term cure while avoiding the immunological complications associated with allogeneic bone marrow transplantation.

Other names

p47-phoxNCF-47KNOXO2Neutrophil NADPH oxidase factor 1Chronic granulomatous disease autosomal 1NCF1 gene therapy

Ex vivo gene addition to autologous hematopoietic stem cells to restore functional p47-phox protein expression and NADPH oxidase activity in derived myeloid cells.