The long term correction of sickle cell anaemia and thalassaemia by gene therapy requires the stable integration of a fully functional a- or beta-globin gene into the genome of a sufficient number of bone marrow (stem) cells of the patient. To achieve this two major problems will have to be addressed, namely stable delivery and expression. At present the efficient introduction and stable integration of genes into a host cell genome can be achieved with known retroviral and adeno associated viral (AAV) vectors. The most efficient elements to express a gene in a stable manner are LCR's. The objective of this proposal is to construct a LCR containing beta-globin transcription unit and viral vector technology that could lead to gene therapy clinical trials. As an attractive alternative we will also start the development of a non viral gene transfer system based on ligand mediated gene transfer. This system has the potential advantage that it has less size constraints and that it can be produced on large scale.
Funding SchemeCSC - Cost-sharing contracts
ST5 5SP Keele
SE1 9RT London