Towards improved yet regulated gene therapy for X-CGD

In this issue of Blood, Wong et al(1) exploit bioinformatic tools to design and test a minimal (core) promoter region to produce sufficient physiological expression of the CYBB gene, which is defective in patients affected by X-linked chronic granulomatous disease (X-CGD). X-CGD is the most common form of CGD in males. CGD is an inborn error of immunity caused by a defective reduced NAD phosphate (NADPH) complex, which is a key component of innate immune defense against bacterial and fungal pathogens.(2) The gp91(phox) protein encoded by the CYBB gene is required for the production of reactive oxidase species and is expressed predominantly in myeloid and B-cell lineages but not in primitive hematopoietic stem and progenitor cells (HSPC).(2)