Functional correction of Fanconi anemia group C hematopoietic cells by theuse of a novel lentiviral vector

Lentiviral vectors transduce nondividing hematopoietic cells more efficient ly than other currently available vector systems. Here we report the result s of human hematopoietic cell gene transfer using lentiviral vectors based upon human immunodeficiency virus (HIV-1) and equine infectious anemia viru s (EIAV). EIAV is a nonprimate lentivirus and is severely restricted in its host range to horses and closely related equines. We employed the EIAV vec tor system to test for gene transfer to human Fanconi anemia (FA) hematopoi etic cells by comparison with HIV-1- and Moloney murine leukemia virus-base d systems. Fanconi anemia is characterized by bone marrow failure secondary to stem cell dysfunction. Fanconi anemia group C EBV-transformed lymphobla sts were transduced with all three viral vectors. Phenotypic correction of FA cells, as measured by mitomycin C drug resistance, was observed with a s imilar efficiency in all vector systems. This is the first description of l entiviral correction of FA cells and suggests that lentiviral vectors may b e useful for FA gene transfer.