@article{discovery1555497,
         journal = {Molecular Therapy},
            year = {2017},
           title = {Lentiviral Vectors with Cellular Promoters Correct Anemia and Lethal Bone Marrow Failure in a Mouse Model for Diamond-Blackfan Anemia},
           month = {August},
          number = {8},
           pages = {1805--1814},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {25},
             url = {http://doi.org/10.1016/j.ymthe.2017.04.002},
            issn = {1525-0024},
          author = {Debnath, S and Jaako, P and Siva, K and Rothe, M and Chen, J and Dahl, M and Gaspar, HB and Flygare, J and Schambach, A and Karlsson, S},
        abstract = {Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1{\ensuremath{\alpha}} short promoter, with or without the locus control region of the {\ensuremath{\beta}}-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia. The findings demonstrate that these vectors rescue the proliferation defect and improve erythroid development of transduced RPS19-deficient bone marrow cells. Remarkably, bone marrow failure and severe anemia in Rps19-deficient mice was cured with enforced expression of RPS19 driven by the elongation factor 1{\ensuremath{\alpha}} short promoter. We also demonstrate that RPS19-deficient bone marrow cells can be transduced and these cells have the capacity to repopulate bone marrow in long-term reconstituted mice. Our results collectively demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia using lentiviral vectors with cellular promoters that possess a reduced risk of insertional mutagenesis.},
        keywords = {Diamond-Blackfan anemia, gene therapy, lentiviral vectors}
}