Producing and evaluating a novel lentiviral vector for β-thalassaemia gene therapy

The β-haemoglobinopathies are of the most prevalent inherited disorders worldwide. β-thalassaemia is a single gene disorder affecting the β-globin gene, thus resulting in a lack or depleted availability of β -globin for formation of haemoglobin. β-thalassaemia has become a target for gene therapy based treatments in hope of a cure, or significant phenotype amelioration. The technique aims to treat the haematopoietic stem cells (HSC) of patients with the viral vectors ex vivo, in the hope of significant β -globin mRNA transcript production on HSC erythroid differentiation post re-transplantation. Numerous investigations have been conducted in the use of Lentiviral vectors harbouring human β-globin transcription units, only one of which has proceeded into clinical trials (Cavazzana-Calvo, Payen et al. 2010). The ultimate aim of all 'construct' designs is to present significant phenotype amelioration with an average of one vector copy number (VCN) per HSC.