Base editing of blood stem cells to fix the CYBB mutation in X-linked chronic granulomatous disease.

* INCLUSION CRITERIA:

  -\>= 18 years of age.
* Confirmed CYBB c.676 C\>T mutation.
* Male patients.
* Clinically stable and eligible to undergo apheresis and conditioning chemotherapy.

  -\>=5 x 10\^6 cryopreserved cells/kg body weight available for study product manufacturing.
* History of at least one prior serious infection or inflammatory complication requiring hospitalization despite conventional therapy.
* In the experience of a qualified clinical investigator, the patient has a poor prognosis.
* Able and willing to use a highly effective method of contraception, AND partner has communicated her willingness through subject to do same, if engaging in potentially reproductive sex from the signing of the informed consent and for 6 months after IMP infusion. Acceptable methods of contraception include the following:

  * Hormonal contraception in continuously effective use by female partner.
  * Male or female condom with spermicide as indicated.
  * Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide by female partner.
  * Intrauterine device in-situ throughout above period by female partner.

EXCLUSION CRITERIA:

Individuals meeting any of the following criteria will be excluded from study participation:

* Untreated, acute infection.
* Elevated anti-gp91 specific autoantibodies \>2 x ULN
* Elevated anti-gp91 specific T cells (\>10 fold)
* Anti-platelet antibody screening with \>1 anti-platelet antibody positive in the presence of an ongoing brain infection; OR \>1 anti-platelet antibody positive and considered unsafe for study participation after consultation with hematology specialist.
* Known hypersensitivity to busulfan or any component of the product.
* Contraindications for administration of busulfan.
* Any current or pre-existing hematologic malignancy.
* Chronic infections that are considered unsafe for participation in the study by Infectious Disease Consultant.
* Cardiac abnormalities and neurological abnormalities that are deemed unsafe to participate in the study.
* Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).
* Hematological parameters unsafe for apheresis or above Grade 2 Common Terminology Criteria for Adverse Events (CTCAE) criteria until improved.
* Hepatic dysfunction- alanine aminotransferase (ALT \>3.0 - 5.0 x upper limit of normal \[ULN\]), aspartate aminotransferase (AST \>3.0 - 5.0 x ULN), bilirubin (\>1.5 - 3.0 x ULN).
* Renal dysfunction-serum creatinine \>1.5 - 3.0 x ULN or creatinine clearance 59-30 mL/min/1.73 m\^2.
* Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time \>2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).
* Uncontrolled hypertension- Systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg.
* Abnormal blood chemistries- Hyperkalemia (K \>5.5 - 6.0 mmol/L), Hypokalemia (\<LLN - 3.0 mmol/L and requiring intervention); OR Hypercalcemia (corrected serum calcium \>11.5 - 12.5 mg/dL), Hypocalcemia (corrected serum calcium \<8.0 -7.0 mg/dL)

These values exclude false abnormalities secondary to hemolysis.

* Cytogenetic abnormalities evidenced on bone marrow aspirate.
* Pulmonary dysfunction FEV1\<25% predicted.
* Previous treatment with gene therapy or gene editing products.
* Previous receipt of non-HLA matched donor granulocyte transfusions.
* Any other condition that, in the opinion of the investigator, may unduly compromise the safety or compliance of the patient, or would make successful study completion highly unlikely.
* Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.

NOTE: Alemtuzumab (campath) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore, no gene therapy will occur on this protocol.