Cancer risk clouds gene cures

DESPITE its spectacular achievements, the first successful form of gene therapy will for now be used only as a last resort due to the risk of cancer. And that's not the only bad news. The latest studies suggest that some other gene therapies using different viruses might also trigger cancer.

The Necker Hospital in Paris pioneered the use of gene therapy to cure the severe inherited immune disease called X-SCID. But two of the 11 boys treated have developed leukaemia. Both these cases appear to be due to the corrective gene being inserted near another gene called Lmo2, which helps control cell growth and can contribute to cancer if turned on at the wrong time (New Scientist, 25 January, p 12).

Calculations by Christof von Kalle of the University of Cincinnati College of Medicine in Ohio suggest that rather than being an extraordinary coincidence the engineered mouse retrovirus used to deliver the gene in the French studymay insert it near Lmo2 about once per 100,000 insertions. Since millions of bone marrow cells are modified and returned to the boys, such insertions may crop up in most if not all of the patients.

The added gene has now turned up near Lmo2 in a third child in the French trial, von Kalle last week told a gene therapy conference in Banff, Canada. Fortunately, the boy shows no signs of leukaemia, suggesting that a further genetic defect may be necessary to trigger uncontrolled growth of the modified cells.

Gene therapists are still hoping that this problem will prove specific to the gene or methods used in the X-SCID therapy. But experiments done by Frederic Bushman of the Salk Institute near San Diego suggests there could also be a potential problem with HIV and other related retroviruses, which many researchers are planning to use in gene therapy.

Bushman infected human cells with the viruses and looked to see where they landed. Last year, he reported that the viruses are more likely to land in genes- especially in active on

Contact: Claire Bowles
New Scientist

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