Fanconi anemia (FA) is an inherited recessive DNA repair disorder mainly 
characterized by bone marrow failure and cancer predisposition. Studies in 
mosaic FA patients have shown that reversion of one inherited germ-line mutation 
resulting in a functional allele in one or a few hematopoietic stem cells (HSCs) 
can lead to the proliferation advantage of corrected cells, thus over time 
normalizing the hematologic status of the patient. In contrast to these 
observations, it is still unclear whether ex vivo genetic correction of FA HSCs 
also provides a similar proliferation advantage to FA HSCs. Using an FA mouse 
model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27)) 
mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs 
results in the progressive expansion of genetically corrected clones in 
mild-conditioned FA-D1 recipients. Consistent with these data, hematopoietic 
progenitors from FA recipients progressively became mitomycin C resistant and 
their chromosomal instability was reverted. No evidence of myelodysplasia, 
leukemias, or abnormal clonal repopulation was observed at multiple time points 
in primary or secondary recipients. Our results demonstrate that ectopic 
expression of BRCA2 confers a beneficial in vivo proliferation advantage to 
FA-D1 HSCs that enables the full hematopoietic repopulation of FA recipients 
with genetically corrected cells.