Current status of globin gene therapy for the treatment of β-thalassaemia Journal Article
| Authors: | Lisowski, L.; Sadelain, M. |
| Article Title: | Current status of globin gene therapy for the treatment of β-thalassaemia |
| Abstract: | β-Thalassaemia major is a congenital anaemia for which there is presently no curative therapy other than allogeneic haematopoietic stem cell transplantation. This therapeutic option, however, is not available to most subjects for whom there is no available human leucocyte antigen-matched bone marrow donor. The transfer of a regulated globin gene in autologous haematopoietic stem cells is therefore a direly needed alternative treatment. This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation- and stage-restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, it has been demonstrated that an optimized combination of proximal and distal transcriptional control elements permits lineage-specific and elevated β-globin expression in vivo, resulting in the correction of anaemia and secondary organ damage in β-thalassaemic mice. Several groups have extended these findings to various models of β-thalassaemia and sickle cell disease. Different globin vectors, however, do not express β-globin at the same level, and accordingly require the delivery of markedly different vector copy numbers to correct anaemia. Insulators are under investigation to assess whether they might enhance globin gene expression or vector safety. Altogether, recent advances in globin vector design bode well for upcoming clinical trials to assess the therapeutic value of globin gene transfer. © 2008 The Authors. |
| Keywords: | promoter region; gene deletion; drug efficacy; drug safety; nonhuman; conference paper; gene expression; intron; in vivo study; cell differentiation; drug design; viral gene delivery system; genetic vectors; gene expression regulation; hla matching; transcription regulation; gene therapy; lentivirus; lentivirus vector; retrovirus vector; beta thalassemia; stem cell gene therapy; transgene; beta-thalassemia; allogeneic hematopoietic stem cell transplantation; gene silencing; retroviridae; lentiviral vectors; globins; gene transfer techniques; beta globin; genetic regulation; hemoglobinopathy; iron overload; viral gene therapy; erythroid-specific expression; globin gene expression; stem cell therapy; thalassaemia; insulator element; insulator elements |
| Journal Title: | British Journal of Haematology |
| Volume: | 141 |
| Issue: | 3 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2008-05-01 |
| Start Page: | 335 |
| End Page: | 345 |
| Language: | English |
| DOI: | 10.1111/j.1365-2141.2008.07098.x |
| PUBMED: | 18410569 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: BJHEA" - "Source: Scopus" |
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