Understanding fetal globin gene expression: A step towards effective HbF reactivation in haemoglobinopathies

The ability to perturb ontogeny and prevent or reverse the fetal/adult switch in globin gene subtype offers therapeutic hope in the haemoglobinopathies. Study of normal development globin gene expression, HPFH and pharmacological induction of HbF all provide insights into how this may be achieved. In the next decade, drug development programmes and the use of trans-acting genes in gene therapy will be expanded, utilizing models of haemoglobin switching. Complementary to this will be the search for additional factors which influence the temporal profile of the globin genes and further study of gene transfer efficiency, control of transgene expression, and stem cell expansion and transplantation. Advances in all these areas will bring the reactivation of fetal haemoglobin closer as a therapeutic modality in SCD and β-thalassaemia.