Similarly, molecular techniques can be applied in a therapeutic setting to introduce functional copies of defective genes into cells that reconstitute the immune system. These are the first steps towards somatic gene therapy for primary immunodeficiencies and other bone marrow related disorders. Our aim has been to develop the technology which will allow us to introduce a normal copy of the relevant gene into the patient's own bone marrow before transplantation into the patient. This should eliminate many of the problems associated with transplantation, including rejection and graft versus host disease. Clinical trials using this novel therapy are being planned in the near future.
Retroviral vectors are the most widely used vehicles for somatic gene therapy to date.
However problems, including inefficient transduction of HSC, requires the development of improved retroviral vectors, including pseudotyped vectors. Novel vectors, containing tissue specific promoters to direct expression, and modified packaging cell lines are being developed. The use of alternate virus vectors, including lentiviral vectors, are being investigated. These vectors have the advantage of being able to integrate their genetic material into quiescent cell types, including HSCs. In the early embryo, this region has been found to contain a cluster of cells closely associated with the ventral endothelium of the dorsal aorta.