Lentiviral Gene Therapy for X-linked Severe Combined Immunodeficiency

Inclusion Criteria:

1. Diagnosis of SCID-X1 based on immunophenotype and lack of T cell function (proliferation to PHA <10% of the lower limit of normal for the laboratory) ANDconfirmed by a mutation in IL2RG
2. Lack of an HLA identical (A, B, C, DR, DQ) related donor
3. Age <5 years
4. Signed informed consent
5. Documentation of willingness to follow up for 15 years post-infusion
6. If the patient has previously undergone allogeneic transplant or gene therapy,insufficiency of graft-derived T cell engraftment must be documented.
7. Age at least 8 weeks of age by the time of busulfan administration

Exclusion Criteria:

1. Patients with an active, therapy-resistant infection. Infections that are known to behighly morbid in SCID patients will be considered active and therapy-resistant if theinfectious agent is repeatedly isolated despite a minimum of 2 weeks of appropriatetherapy and is associated with significant organ dysfunction (including but notlimited to abnormalities listed below).
2. Mechanical ventilation including continuous positive airway pressure
3. Abnormal liver function defined by AST and ALT >10 times the upper range ofnormal OR Bilirubin >2 mg/dL
4. Shortening fraction on echocardiogram <25% or ejection fraction <50%
5. Renal failure defined as glomerular filtration rate <30 ml/min/1.73 m2 ordialysis dependence
6. Uncontrolled seizure disorder
7. Encephalopathy
8. Documented coexistence of any disorder known to affect DNA repair
9. Diagnosis of active malignant disease other than EBV-associated lymphoproliferativedisease
10. Patients with evidence of infection with HIV-1
11. Previous allogeneic transplant with cytoreductive chemotherapy
12. Major (life-threatening) congenital anomalies. Examples of "major (life-threatening)congenital anomalies" include, but are not limited to: unrepaired cyanotic heartdisease, hypoplastic lungs, anencephaly or other major central nervous systemmalformations, other severe non-repairable malformations of the gastrointestinal orgenitourinary tracts that significantly impair organ function.
13. Other conditions which in the opinion of the P.I. or Co-investigators, contra-indicatecollection and/or infusion of transduced cells or indicate patient's inability tofollow the protocol. These may include for example clinical ineligibility to receiveanaesthesia, severe deterioration of clinical condition of the patient aftercollection of bone marrow but before infusion of transduced cells, or documentedrefusal or inability of the family to return for scheduled visits. There may be otherunforeseen rare circumstances that would result in exclusion of the patient, such assudden loss of legal guardianship.