Current status of globin gene therapy for the treatment of β-thalassaemia Review uri icon

Overview

MeSH Major

  • Genetic Therapy
  • Globins
  • beta-Thalassemia

abstract

  • beta-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 directly 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 beta-globin expression in vivo, resulting in the correction of anaemia and secondary organ damage in beta-thalassaemic mice. Several groups have extended these findings to various models of beta-thalassaemia and sickle cell disease. Different globin vectors, however, do not express beta-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.

publication date

  • May 2008

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2008.07098.x

PubMed ID

  • 18410569

Additional Document Info

start page

  • 335

end page

  • 45

volume

  • 141

number

  • 3