FANCA Gene Transfer for Fanconi Anemia Using a High-safety, High-efficiency, Self-inactivating Lentiviral Vector

Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low. In addition, some patients have physical defects usually involving the skeleton and kidneys. Fanconi anemia is typically diagnosed in childhood, and there is a high fatality rate. Hematopoietic stem cell transplantation (HSCT) is a common treatment for Fanconi anemia. However, there are many risks associated with HSCT including rejection of the transplanted cells and graft-versus-host disease.

The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming immune abnormalities present at the time of treatment, assessment of gene correction efficiency, and finally the long-term correction of Fanconi anemia associated disease symptoms.

Inclusion criteria

• Diagnosis of Fanconi anemia FANCA type based on DNA sequencing and sensitivity test for chromosomal cleavage by mitomycin C or butylene oxide.
• No cytogenetic abnormalities and the proportion of myelodysplastic abnormalities does not exceed 5% within 3 months prior to stem cell collection.
• Age: ≥ 4 years.
• Karnofsky: ≥ 70%.
• ANC ≥ 5×10^8/L; PLT ≥ 2×10^10/L.
• Hemoglobin ≥ 8g/dL.
• Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

• serum creatinine ≤ 1.5×ULN;
• serum bilirubin ≤ 3×ULN;
• AST/ALT ≤ 5×ULN.
• Pulmonary function is normal; DLCO > 50%.
• Written, informed consent obtained prior to any study-specific procedures.

Exclusion criteria

• Diagnosis of active malignant disease or myelodysplastic syndrome.
• Diagnosis of myeloid leukemia.
• Pregnant or lactating females.
• Existence of an available HLA-identical related donor.
• Subject infected with HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
• Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.