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Haemophilia, usually caused by mutations in the X-linked gene encoding the factor VIII protein and affecting about 1 in 5000 males, is thought to be a good candidate for gene therapy. For example, the condition can be improved even by very low levels of factor VIII, and there are no organ-targeting problems, as all that is needed is for the protein to circulate in the bloodstream. Several groups have attempted gene therapy for haemophilia using engineered viruses to introduce the gene into cells, and some success has been reported with this approach. Roth et al have used a different technique: they isolated skin cells from each patient, used an electrical treatment (electroporation) to induce the cells to take up factor VII-encoding DNA, cultured clones of engineered cells and then implanted a suitable clone into the abdominal cavity of the patient [Roth, D.A. et al (2001) N Engl J Med 344, 1735-1742]. The patients were monitored over a period of two years. The trial was a Phase 1 trial to monitor the safety of the treatment, but some subjective measures of efficacy were also recorded: of six patients treated, four experienced some improvement, as assessed by decreased use of factor VIII treatment and a decrease in the frequency of episodes of spontaneous bleeding. The implanted cells produced factor VIII protein at levels of up to 2% of normal for the first few months, but expression of the gene had disappeared after 10 months.

Comment: These results are very preliminary and much more work is needed before it will be clear whether this approach will have a place in the treatment of haemophilia. Some of the outstanding problems are discussed in an editorial by Miller and Stamatoyannopoulos [Miller, D.G. and Stamatoyannopoulos, G. (2001) N Engl J Med 344, 1782-1783]. As well as the need to prolong expression of the factor VIII gene in the transplanted cells, there are questions about the safety of such implants, which could cause inflammatory responses or even become cancerous.