Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin Journal Article
| Authors: | May, C.; Rivella, S.; Callegari, J.; Heller, G.; Gaensler, K. M. L.; Luzzatto, L.; Sadelain, M. |
| Article Title: | Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin |
| Abstract: | The stable introduction of a functional β-globin gene in haematopoietic stem cells could be a powerful approach to treat β-thalassaemia and sickle- cell disease. Genetic approaches aiming to increase normal β-globin expression in the progeny of autologous haematopoietic stem cells might circumvent the limitations and risks of allogeneic cell transplants. However, low-level expression, position effects and transcriptional silencing hampered the effectiveness of viral transduction of the human β-globin gene when it was linked to minimal regulatory sequences. Here we show that the use of recombinant lentiviruses enables efficient transfer and faithful integration of the human β-globin gene together with large segments of its locus control region. In long-term recipients of unselected transduced bone marrow cells, tetramers of two murine α-globin and two human β(A)-globin molecules account for up to 13% of total haemoglobin in mature red cells of normal mice. In β-thalassaemic heterozygous mice higher percentages are obtained (17% to 24%), which are sufficient to ameliorate anaemia and red cell morphology. Such levels should be of therapeutic benefit in patients with severe defects in haemoglobin production. |
| Keywords: | protein expression; nonhuman; animal cell; mouse; animals; mice; cell line; animalia; genetic vectors; transduction, genetic; recombinant proteins; gene therapy; lentivirus; beta thalassemia; beta-thalassemia; murinae; bone marrow transplantation; hemoglobins; hiv-1; lentivirinae; globins; gene transfer techniques; sickle cell anemia; hemoglobin synthesis; humans; male; female; priority journal; article; beta globulin |
| Journal Title: | Nature |
| Volume: | 406 |
| Issue: | 6791 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2000-07-06 |
| Start Page: | 82 |
| End Page: | 86 |
| Language: | English |
| DOI: | 10.1038/35017565 |
| PUBMED: | 10894546 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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