Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome 
characterized by a specific deficiency in erythroid progenitors. Forty percent 
of the patients are blood transfusion-dependent. Recent reports show that the 
ribosomal protein S19 (RPS19) gene is mutated in 25% of all patients with DBA. 
We constructed oncoretroviral vectors containing the RPS19 gene to develop gene 
therapy for RPS19-deficient DBA. These vectors were used to introduce the RPS19 
gene into CD34(+) bone marrow (BM) cells from 4 patients with DBA with RPS19 
gene mutations. Overexpression of the RPS19 transgene increased the number of 
erythroid colonies by almost 3-fold. High expression levels of the RPS19 
transgene improved erythroid colony-forming ability substantially whereas low 
expression levels had no effect. Overexpression of RPS19 had no detrimental 
effect on granulocyte-macrophage colony formation. Therefore, these findings 
suggest that gene therapy for RPS19-deficient patients with DBA using viral 
vectors that express the RPS19 gene is feasible.