Chapter 9. Gene Therapy for Severe Combined Immunodeficiency

Summary

Severe combined immunodeficiency (SCID) represents a group of inherited disorders characterised by a reduction or absence of T lymphocyte function. Many of the molecular lesions are known and these disorders have become model systems for testing gene therapy protocols. Adenosine deaminase deficiency is treated with enzyme replacement and the results suggest that simple gene expression systems may be efficacious for this condition. The first approved clinical trial of gene therapy involved repeated ex vivo transduction of autologous T cells with a retroviral vector expressing human ADA, followed by expansion and reinfusion into two patients. It demonstrated the potential of this therapy and suggested some clinical benefit. Further studies have targeted haemopoietic stem cells, again with indications of success. Such cells are relatively quiescent and umbilical cord blood cells may be better targets. Alternatively, one could use vectors such as adeno-associated virus that transduce quiescent cells.