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THE talents of two killer viruses, HIV and Ebola, may one day be combined to
create a powerful new type of gene therapy for cystic fibrosis and other lung
diseases.

Cystic fibrosis is a hereditary disease that causes premature death by
clogging the lungs and gut with mucus. About 6500 people in Britain have the
condition. The aim of gene therapy is to restore normal function to the affected
cells by delivering working genes via genetically engineered viruses.

But few viruses are able to successfully infect most cells of the airways
because these cells divide slowly or not at all. Viruses that could persist in
these sluggish cells lack the envelope proteins on their surface necessary for
them to attach to the cells and get inside.

So Gary Kobinger and colleagues at the University of Pennsylvania in
Philadelphia decided to combine the attributes of more than one virus. They
started with the core of HIV, a virus which persists even in non-dividing cells
by integrating into the cell鈥檚 chromosomes. Because HIV cannot infect lung
tissue efficiently, the researchers engineered their virus to have envelope
proteins from a variety of respiratory viruses, including influenza and the
Zaire strain of Ebola. They crippled the hybrid virus to make it safe. 鈥淚t鈥檚 a
novel approach that definitely delivers the gene payload to the lung,鈥� says
Pamela Davis, a cystic fibrosis researcher at Case Western Reserve University in
Cleveland, Ohio.

When Kobinger and his colleagues applied the HIV-Ebola hybrid to human lung
cells grown in the lab, they found that the hybrid infected at least eight times
as many cells as any other virus they tested. Tests on live mice showed that 63
days after exposure to the virus, the marker gene was still active in 24 per
cent of lung cells. The team plans to test the ability of the cells to infect
monkeys鈥� lungs. But Davis says it remains unclear whether this virus could
penetrate the mucus that coats the lungs of cystic fibrosis patients.

And if it is successful, convincing the public that the two notorious killers
have medical benefits won鈥檛 be easy. 鈥淲hen I presented this work at a meeting,
people actually laughed,鈥� Kobinger says. 鈥淭hey realised this would be a hard
蝉别濒濒.鈥�