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New technique to make gene therapy more efficient

SCRUNCHING UP DNA into ultra-tiny balls could be the key to making gene therapy safer and more efficient. The technique is now being tested on people with cystic fibrosis.

So far, modified viruses have proved to be the most efficient way of delivering DNA to cells to make up for genetic faults. But viruses can't be given to the same person time after time because the immune system starts attacking them. Viruses can also cause severe reactions.

As a result, researchers increasingly favour other means of delivering genes, such as encasing DNA in fatty globules called liposomes that can pass through the membranes round cells. But simply getting a gene into a cell isn't enough-for the desired protein to be produced, you need to get the gene into the cell's nucleus.

At around 100 nanometres in size, most liposomes are too large to pass through the tiny pores in the nuclear membrane except when the membrane breaks down during cell division. Even if cells are rapidly dividing, delivering genes via liposomes isn't very efficient-and it's no good for slowly dividing cells such as those lining the lungs.

But researchers at Case Western Reserve University and Copernicus Therapeutics, both in Cleveland, Ohio, have developed a way to pack DNA into particles 25 nanometres across, small enough to enter the nuclear pores. The nanoparticles consist of a single DNA molecule encased in positively charged peptides and are themselves delivered to cells via liposomes. In cells grown in culture, there was a 6000-fold increase in the expression of a gene packaged this way compared with unpackaged DNA in liposomes.

Trials have now begun in 12 people with cystic fibrosis, who have a faulty gene that means thick mucus accumulates in their lungs. The researchers will first test the technique on nasal cells before trying to deliver genes to the lungs.

"We're very excited about this," says Robert Beall, president of the Cystic Fibrosis Foundation.
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Contact: Claire Bowles
claire.bowles@rbi.co.uk
44-207-331-2751
New Scientist
8-May-2002


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