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Can two killers make a cure?

Regulators in the US could soon be asked to approve a human trial of gene therapy for cystic fibrosis that uses a hybrid of the HIV and Ebola viruses. Tests on monkeys show the hybrid virus delivers genes to the lungs far more efficiently than any other method developed so far. And while the idea of combining two killer viruses sounds horrifying, the risks should be low.

Despite much effort, no one has managed to develop an effective form of gene therapy to treat the lung problems of people with cystic fibrosis. The condition is caused by a mutation in the CFTR gene, and one of the problems in developing a treatment is getting a working version of CFTR into a high enough proportion of cells to restore normal lung function.

While HIV is good at adding genes to cells' genomes, it does not target lung epithelial cells. Ebola binds strongly to these cells, so Gary Kobinger at the University of Pennsylvania in Philadelphia tried adding a surface protein from Ebola to HIV. Initial tests on mice showed the hybrid virus was very efficient: the gene it carried was active in 24 per cent of airway cells after two months, a far better proportion than achieved by other delivery methods (New Scientist, 10 March 2001, p 19).

But will it work in humans? The team has now done the next best thing and used the hybrid virus to deliver a test gene, lacZ, to the lungs of monkeys. After two months the gene was active in 21 per cent of cells, Kobinger told New Scientist. He is preparing the results for publication.

"The gap between monkeys and humans is much smaller than from mice to monkeys," says Ray Pickles, a gene therapy researcher at the University of North Carolina, Chapel Hill. "This could be in human trials pretty soon."

Kobinger now plans a more extensive monkey trial to convince the US Food and Drug Administration that human trials will be safe. The hybrid virus is created by adding HIV RNA, a stripped-down version of the Ebola surface prot
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Source:New Scientist Boston office


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