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

Background: CGD is caused by a gene mutation. For people with CGD, their cells cannot kill germs well, so they can get frequent or life-threatening infections. Researchers want to see if a new procedure can help a person s cells kill germs for a short time. It uses messenger RNA (mRNA) to deliver correct instructions for the gene mutation to the cells. Objective: To test a procedure in which mRNA is added to a person s blood cells. Eligibility: Males aged 18-75 with CGD with a mutation in the gene that makes the protein gp91phox. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Swab to test for strep throat Some screening tests will be repeated during the study. Participants will be admitted to the NIH Clinical Center hospital for at least 7 days. They will have apheresis. For this, a medicine is injected under their skin to prepare their white blood cells for collection. An IV line is placed into an arm vein. Blood goes through the IV line into a machine that divides whole blood into red blood cells, plasma, and white blood cells. The white blood cells are removed, and the rest of the blood is returned to the participant through an IV line in their other arm. The next day, they will get their mRNA-corrected cells via IV. They will be monitored for 3 more days. After discharge, participants will keep a symptom diary. They will be contacted weekly for one month, and then once a month. They will have a follow-up visit 3 months after the infusion.

* INCLUSION CRITERIA: Individuals must meet all of the following criteria to be eligible for study participation: * Males aged 18 to 75 years * CGD confirmed by DHR and 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 CGD-Grans infusion. Acceptable methods of contraception include the following: * Hormonal contraception * Male or female condom EXCLUSION CRITERIA: Individuals meeting any of the following criteria will be excluded from study participation: * Clinically unstable due to moderate to severe acute systemic infections as defined by persistent resting tachypnea, tachycardia, or hypoxia of \>20% from baseline and hypotension. * Current or history of stage 4 chronic kidney disease or estimated glomerular filtration rate \[eGFR\] \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. * 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. NOTE: For prospective subjects who, per PI assessment at screening, have abnormal liver function tests, and/or a significant history of liver disease, and/or liver-related complications of CGD, and who otherwise meet eligibility criteria \[i.e. those who do NOT meet any of the exclusion set forth herein\], a hepatology consult will be required at screening, and participation must be approved in writing by hepatology to the PI. * Electrocardiogram abnormalities indicative of acute myocardial injury, or arrhythmias that presents anesthetic risks, at screening. * Anemia with hemoglobin \