Chapter 12. Therapeutic Approaches to Haemoglobinopathies

Summary

β Thalassaemia and sickle cell disease were early targets for gene therapy because the β globin gene is small and well characterised, the target haemopoietic stem cell is easily obtainable and mouse models had been cured by transfer of the human globin gene. After early attempts were unsuccessful, basic studies were undertaken to improve the efficiency of gene transfer and expression. Retroviral vectors have been designed that generate high titre and stable, high levels of β globin gene expression in vitro. Transfer of the Aγ globin gene via adeno-associated viral vectors has led to long-term expression of the human gene in primary transplants. Correction of defective globin genes by homologous recombination for the treatment of thalassaemia has been achieved in cell lines and in stem cells ex vivo. Other indirect gene therapies include correction of abnormal splicing, activation of compensating genes, erythropoietin gene transfer and reduction of a globin gene expression.