NADPH Oxidase Correction in mRNA-transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)

Eligibility Criteria

• * Males aged 18 to 75 years
• * CGD confirmed by DHR and gp91phox-deficiency subtype confirmed by protein analysis and/or genetic sequencing
• * Has a physician at home for follow-up care
• * Able to provide informed consent
• * For men who engage in activities that can result in pregnancy, agree to use contraception when engaging in sexual activities that can result in pregnancy. Contraception must be used from screening through 3 months after the gp91-Grans infusion. Acceptable methods of contraception include the following:
• * Hormonal contraception
• * Male or female condom
• * Evidence of moderate to severe systemic infections as defined by any of the following:
• * Fevers \>=39 (Infinite)C within 3 days of treatment.
• * Absolute neutrophil count (ANC) \>12,000/microliter at screening (some CGD patients may chronically have ANC higher than the upper limit of normal value and not have a systemic infection).
• * Standard clinical diagnosis (by any imaging technology) of pneumonia, liver abscess, or other deep tissue abscess (other than chronic anal fissures or fistula or superficial skin or subcutaneous infections, which are allowable for this trial) at screening.
• * Positive blood culture within 2 weeks of treatment.
• * Receipt of a high-dose steroid, equivalent to \>1 mg/kg/day of prednisone, within 30 days of screening. There is a high percentage of CGD patients with inflammatory bowel disease on \>0.5 mg/kg/day maintenance prednisone.
• * Current or history of stage 4 chronic kidney disease or estimated glomerular filtration rate
• * Unstable diabetes mellitus with hemoglobin A1c \>7.0% and fasting serum glucose \>200 mg/dL at screening.
• * Current or history of heart failure stage D as defined by the American College of Cardiology Foundation/American Heart Association guidelines.
• * History of arrhythmias that are symptomatic and deemed clinically unsafe for participation by NIH CC Cardiology consultation.
• * Current or history of invasive cancers that require chemotherapy within 5 years of screening.
• * Evidence of urinary tract infection at screening.
• * Evidence of streptococcal pharyngitis at screening.
• * Active hepatitis B, C, or HIV infections at screening.
• * Unstable hypertension requiring addition of new anti-hypertensives within 2 weeks of screening.
• * Impaired renal function that is unstable, with serum creatinine \>3.0 mg/dL and rising.
• * Serum transaminases and bilirubin that are \>3 x the upper limit of normal.
• * Electrocardiogram abnormalities indicative of acute myocardial injury, or arrhythmias that presents anesthetic risks, at screening.
• * Anemia with hemoglobin \<8 g/dL (transfusions to correct anemia permitted).
• * Thrombocytopenia (platelets \<50 x10\^9 cells/L) (platelet transfusions to correct thrombocytopenia permitted).
• * Profound thrombocytopenia (platelet counts \<10,000/microliter) that is not reversible with platelet transfusions.
• * Abnormal prothrombin time/partial thromboplastin time (PT/PTT) values outside the ranges accepted at the NIH CC that are not corrected or that cannot be attributed to presence of Lupus anticoagulant (commonly found in CGD patients).
• * Inherited bleeding disorder that precludes line placement.
• * Severe oxygen-dependent pulmonary disease that increases risks of procedures that may require sedation.
• * History of or current evidence of alcohol or illicit drug abuse or dependence.
• * Participation in a clinical protocol that includes an intervention that, in the opinion of the investigator, may affect the results of the current study.