Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.
Author
Summary, in English
Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic progenitors from ribosomal protein S19-deficient patients in vitro and in vivo following xenotransplantation. However, studies using animal models are needed to assess the therapeutic efficacy and safety of the viral vectors. In the present study we have validated the therapeutic potential of gene therapy using mouse models for ribosomal protein S19-deficient Diamond-Blackfan anemia. Using lentiviral gene transfer we demonstrate that enforced expression of ribosomal protein S19 cures the anemia and lethal bone marrow failure in recipients transplanted with ribosomal protein S19-deficient cells. Furthermore, gene-corrected ribosomal protein S19-deficient cells showed an increased pan-hematopoietic contribution over time compared to untransduced cells without signs of vector-mediated toxicity. Our study provides a proof of principle for the development of clinical gene therapy to cure ribosomal protein 19-deficient Diamond-Blackfan anemia.
Department/s
- Division of Molecular Medicine and Gene Therapy
- Department of Experimental Medical Science
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
Publishing year
2014
Language
English
Pages
1792-1798
Publication/Series
Haematologica
Volume
99
Issue
12
Links
Document type
Journal article
Publisher
Ferrata Storti Foundation
Topic
- Hematology
Status
Published
ISBN/ISSN/Other
- ISSN: 1592-8721