Liposomes--hollow, microscopic spheres that fat molecules spontaneously form when they’re in solution--are a gentler type of gene bullet. Natasha Caplen and her colleagues at Royal Brompton Hospital in London are experimenting with liposomes as a gene-therapy vehicle for cystic fibrosis. People with CF have a defect in the gene for a protein that regulates the flow of chloride ions in and out of cells; as a result, chloride ions become trapped in the cells of the respiratory tract, as does water, and the lungs become clogged with dry, sticky mucus. In two separate gene-therapy trials, the healthy gene has been successfully delivered to cells in the lungs and nose by a virus. But some patients have suffered inflamed lungs or swollen, itchy nostrils, which just worsens their breathing problems.
In Caplen’s experiments, liposomes were coated with the healthy CF gene and sprayed into patients’ nostrils. Cells lining the nose absorbed the liposomes by forming membrane pockets (called endosomes) around them, and some copies of the gene made their way into the cells’ nuclei. Measurements of the patients’ chloride ion levels indicated that the liposomes had delivered the gene--and without the side effects caused by viruses. With the virus, they saw inflammation at the therapeutic dose, says Leaf Huang, a pharmacologist at the University of Pittsburgh who collaborated with Caplen’s team. We don’t. To actually treat CF, the researchers will have to deliver the liposomes to the lungs by having the patients inhale deeply from a breathing mask.